Objective: The aim of our study was to explore the inhibition and apoptosis-inducing effect of the combination of Huaier aqueous extract with recombinant human Endostatin and DDP in human lung adenocarcinoma A549 cell...Objective: The aim of our study was to explore the inhibition and apoptosis-inducing effect of the combination of Huaier aqueous extract with recombinant human Endostatin and DDP in human lung adenocarcinoma A549 cells. We also investigated the reversal effect of Huaier aqueous extract in reversing cisplatin resistance in human lung adenocarcinoma A549/DDP cells. Methods: We treated A549 cells with Huaier aqueous extract and the combination of Huaier aqueous extract and DDP or rh-Endostatin for 24 h, 36 h and 48 h. And then we calculated the inhibition rate through MTT approach and detected the apoptosis rate by flow cytometry. We also treated A549 and A549/DDP cells with DDP, Huaier aqueous extract, DDP and Huaier aqueous extract for 72 h, respectively. Results: Huaier aqueous extract can inhibit the growth of A549 cells and the inhibition rate improved with the increase of the concentration. The inhibition rate of the combination of rh-Endostatin and 4 mg/mL of Huaier aqueous extract in three time points and the combination of rh-Endostatin and 2 mg/mL of Huaier aqueous extract in the time point of 48 h on the growth of A549 cells all improved(P < 0.005). The inhibition rate of the combination of DDP and Huaier aqueous extract with the concentration of 2 mg/mL or 4 mg/mL on the growth of A549 cells all improved(P < 0.005). The combination of Huaier aqueous extract and DDP and the combination of Huaier aqueous extract with rh-Endostatin and DDP can improve the inhibition on the growth of A549 cells(P < 0.005). Conclusion: Huaier aqueous extract has the inhibition and apoptosis-inducing effects on the A549 cells. And the combination of Huaier aqueous extract and rh-Endostatin or DDP has the synergistic effects on the inhibition of A549 cells. The combination of Huaier aqueous extract with rh-Endostatin and DDP has the synergistic effects on the inhibition of A549 cells. Huaier aqueous extract can reverse the cisplatin resistance in human lung adenocarcinoma A549/DDP cells.展开更多
After more than a decade of controversy on the role of stromal cells in the tumor microenvironment,the emerging data shed light on pro-tumorigenic and potential anti-cancer factors,as well as on the roots of the discr...After more than a decade of controversy on the role of stromal cells in the tumor microenvironment,the emerging data shed light on pro-tumorigenic and potential anti-cancer factors,as well as on the roots of the discrepancies.We discuss the pro-tumorigenic effects of stromal cells,considering the effects of tumor drivers like hypoxia and tumor stiffness on these cells,as well as stromal cell-mediated adiposity and immunosuppression in the tumor microenvironment,and cancer initiating cells'cellular senescence and adaptive metabolism.We summarize the emerging data supporting stromal cell therapeutic potential in cancer,discuss the possibility to reprogram stromal cells of the tumor microenvironment for anti-cancer effects,and explore some causes of discrepancies on the roles of stromal cells in cancer in the available literature.展开更多
Objective: To investigate the anti-colon cancer effects of ethylacetate fraction from Orostachys japonicus(0. japonicus) on HT-29 cancer cells. Methods: The viability of HT-29 cells was assayed by the 3-(4,5-dimethylt...Objective: To investigate the anti-colon cancer effects of ethylacetate fraction from Orostachys japonicus(0. japonicus) on HT-29 cancer cells. Methods: The viability of HT-29 cells was assayed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium(MTS) method. Apoptosis induction and cell cycle inhibition were confirmed by fluorescein isothiocyanate and propidium iodide staining using flow cytometry.Morphological changes in the nucleus were observed, using a fluorescence microscope with4',6-diamidino-2-phenylindole(DAPI) nuclear staining. The expression levels of the upstream and downstream proteins involved in the anti-cancer mechanism were confirmed by Western blotting. Results: After treating HT-29 cells with different concentrations of ethylacetate fraction from O. japonicus, the viability of cells decreased in a concentration-dependent manner,while apoptosis induction and apoptotic body formation increased. Cell cycle analysis showed that the arrest occurred at the sub-G_1 and S phase. Among the upstream and downstream proteins involved in anti-cancer activity, the level of B cell lymphoma-2 decreased, and the bcl-2-associated x protein increased. The level of pro-caspase-3, pro-caspase-8, and pro-caspase-9 decreased, while the level of cleaved-caspase-3, cleaved-caspase-8, and cleaved-caspase-9 increased. Moreover, the phosphorylation, that is, activation of extracellular signal regulated kinase 1/2, Jun-N-terminal kinase, and p38 increased. Conclusions: Combining the above results, it is thought that the survival of HT-29 cells is suppressed by ethylacetate fraction from0. japonicus through mitochondrial regulation-induced caspase cascade activation, induction of apoptosis and cell cycle arrest.展开更多
BACKGROUND Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α(HIF-1α)in the immune microenvironment promotes the progression of hepatocellular carcinoma(HCC),leading to enhanced ...BACKGROUND Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α(HIF-1α)in the immune microenvironment promotes the progression of hepatocellular carcinoma(HCC),leading to enhanced drug resistance in cancer cells.Therefore,altering the immunosuppressive microenvironment by improving the hypoxic state is a new goal in improving cancer treatment.AIM To analyse the role of HIF-1α,which is closely related to tumour proliferation,invasion,metastasis,and angiogenesis,in the proliferation and invasion of liver cancer,and to explore the HIF-1αpathway-mediated anti-cancer mechanism of sirolimus(SRL)combined with Huai Er.METHODS Previous studies on HCC tissues identified the importance of HIF-1α,glucose transporter 1(GLUT1),and lactate dehydrogenase A(LDHA)expression.In this study,HepG2 and Huh7 cell lines were treated,under hypoxic and normoxic conditions,with a combination of SRL and Huai Er.The effects on proliferation,invasion,cell cycle,and apoptosis were analysed.Proteomics and genomics techniques were used to analyze the HIF-1α-related signalling pathway during SRL combined with Huai Er treatment and its inhibition of the proliferation of HCC cells.RESULTS High levels of HIF-1α,LDHA,and GLUT-1 were found in poorly differentiated HCC,with lower patient survival rates.Hypoxia promoted the proliferation of HepG2 and Huh7 cells and weakened the apoptosis and cell cycle blocking effects of the SRL/Huai Er treatment.This was achieved by activation of HIF-1αand glycolysis in HCC,leading to the upregulation of LDHA,GLUT-1,Akt/mammalian target of rapamycin(mTOR),vascular endothelial growth factor(VEGF),and Forkhead box P3 and downregulation of phosphatase and tensin homolog deleted on chromosome ten(PTEN)and p27.The hypoxia-induced activation of HIF-1αshowed the greatest attenuation in the SRL/Huai Er(S50+H8)group compared to the drug treatments alone(P<0.001).The S50+H8 treatment significantly downregulated the expression of mTOR and HIF-1α,and significantly reduced the expression of VEGF mRNA.Meanwhile,the combined blocking of mTOR and HIF-1αenhanced the downregulation of Akt/mTOR,HIF-1α,LDHA,and GLUT-1 mRNA and resulted in the downregulation of PTEN,p27,and VEGF mRNA(P<0.001).CONCLUSION SRL increases the anti-cancer effect of Huai Er,which reduces the promotion of hypoxia-induced HIF-1αon the Warburg effect by inhibition of the PI3K/Akt/mTOR-HIF-1αand HIF-1α-PTEN signalling pathways in HCC.展开更多
Taraxasterol(TS)is a naturally occurring pentacyclic triterpenoid extracted from the traditional Chinese herb Taraxacum mongolicum.Previous studies have highlighted its significant roles in exhibiting anti-inflammator...Taraxasterol(TS)is a naturally occurring pentacyclic triterpenoid extracted from the traditional Chinese herb Taraxacum mongolicum.Previous studies have highlighted its significant roles in exhibiting anti-inflammatory,anti-oxidant,and liver protective effects.In the present study,the anti-cancer potential of TS against cervical cancer was investigated,employing network pharmacology techniques,molecular docking,and in vitro experimental validation.TS exhibits its anticancer properties by modulating multiple targets,pathways,and biological processes.In vitro experiments demonstrated the potent inhibitory effects of TS on cancer cell growth and migration,while no significant impact on apoptosis was observed.The primary objective was to elucidate the anti-cancer potential of TS,which is a crucial lead compound in the treatment of cervical cancer.The findings may serve as a basis for the development of novel anticancer therapeutics and medicine-based interventions for cervical cancer.展开更多
Rhodiola rosea,a perennial herb of the genus Rhodiola in the Crassulaceae family,is commonly used to treat depression,fatigue,cancer and cardiovascular diseases.Herbacetin is a natural flavonol compound extracted from...Rhodiola rosea,a perennial herb of the genus Rhodiola in the Crassulaceae family,is commonly used to treat depression,fatigue,cancer and cardiovascular diseases.Herbacetin is a natural flavonol compound extracted from R.rosea plant,with many pharmacological effects such as anti-cancer effect,anti-oxidant effect and anti-inflammatory effect.In this paper,the pharmacological effects and molecular mechanisms of herbacetin were summarized by consulting domestic and foreign literature,in order to provide a theoretical basis for the development and utilization of herbacetin.展开更多
Polysocoharibe-peptide of Coriolus Versicolor (PSP) is a new anti-cancer immunomodulative drug. The present paper reports on the experimental research done with this drug. It was found that PSP had the ability to reco...Polysocoharibe-peptide of Coriolus Versicolor (PSP) is a new anti-cancer immunomodulative drug. The present paper reports on the experimental research done with this drug. It was found that PSP had the ability to recover hemolysin HC50, to increase the weight of the thymus, and increase the alexin of serum C3 and the IgG content of tumor bearing mice. FSP also significantly raised the pha-gocytic activity of macrophages in normal mice. PSP had a significant inhibitory effect on P38S and S180 cells. At the concentration of 1 mg/ml, PSP inhibited the proliferating activity of some human tumor call lines, such as SGC 7901, SPC, SLY and Mei. It had a direct toxic effect on SPC cells. PSP significantly inhibited the synthesis of nucleic acids of Ehrlich ascites carcinoma cells. In addition, PSP was antagonistic to the side effects of chemotherapy and radiotherapy.展开更多
Medicinal mushrooms have been valued as natural sources of bioactive compounds since times immemorial and have been recognized as potential immunomodulating and anti-cancer agents.Their consumption has consistently be...Medicinal mushrooms have been valued as natural sources of bioactive compounds since times immemorial and have been recognized as potential immunomodulating and anti-cancer agents.Their consumption has consistently been shown to have beneficial effects on human health.Cancer is a generic term for several types of diseases that can be chronic and are responsible for a large number of deaths worldwide.Although there has been considerable progress in modern cancer therapy research,difficulties in understanding the molecular behavior of various types of cancers and the numerous side effects experienced by patients from treatments means that this whole subject area is still problematic.Thus,biological immunotherapy using natural bioactive compounds as supportive treatments in conventional cancer therapies has become in vogue.Bioactive metabolites isolated from medicinal mushrooms have shown potential successes in cancer treatment as biological immunotherapeutic agents that stimulate the immune system against cancer cells.They also act as an effective source of anti-cancer agents,capable of interfering with cellular signal transduction pathways linked to cancer development and progression.In this review we compile available data on the characteristics of medicinal mushrooms that appear to be particularly effective as biological immunotherapeutic agents.Major consideration is given to biological constituents and the putative mechanisms of action by which bioactive compounds act on the human body.Consideration is also given to the benefits that have been claimed for the use of mushrooms in treating cancer and the future prospects of using medicinal mushrooms as potent supportive candidate bioagents for treatment of cancers is discussed.展开更多
Objective: There were some experimental researches in vitro, which showed that tanshinonoe (Tan) had cytotoxic activities against some cancer cell lines. But there was no report of anticancer activity of Tan in vivo. ...Objective: There were some experimental researches in vitro, which showed that tanshinonoe (Tan) had cytotoxic activities against some cancer cell lines. But there was no report of anticancer activity of Tan in vivo. This experimental study was performed to confirm the anticancer activity of Tan in vivo. Methods: Hepatic carcinoma H22 bearing mice were treated with DMSO, 5Fu, and Tan, at the end of experiment, the mice were sacrificed, tumor tissues were separated and weighed, and the tumor inhibitory rate was calculated, 3 times of the same experiments were performed. The proliferating kinetics of hepatic carcinoma H22 cells in mice was measured by bromodeoxyuridine labeling in vivo and immunohistochemical staining of the proliferating cell nuclear antigen (PCNA) in tumor tissues. Results: The tumor inhibitory rates of Tan were 50.0%, 38.5%, and 40.6% in 3 experiments, respectively, compared with those of the DMSOtreated control groups, the differences were significant statistically (P<0.01). The Brdu labeling and PCNA positive cells were 51.8±7.9 and 451.1±26.1, respectively, which were significantly lower than those of controls (84.4±24.3, 694.8±117.1) (P<0.01). Conclusion: Tan had anticancer effect on hepatic carcinoma in vivo; The mechanisms of action might be associated with inhibition of DNA synthesis, PCNA expression and DNA polymerase δ activity of tumor cells.展开更多
Toad venom, called as Chan Su in China, is a widely used traditional Chinese medicine(TCM) whose active components are mainly bufadienolides. Chan Su could exhibit cardiotonic, anti-microbial, anti-inflammatory and, m...Toad venom, called as Chan Su in China, is a widely used traditional Chinese medicine(TCM) whose active components are mainly bufadienolides. Chan Su could exhibit cardiotonic, anti-microbial, anti-inflammatory and, most importantly, anti-cancer effects. In the present review, reports about the in vitro, in vivo and clinical anti-cancer effects of Chan Su or its representative component, bufalin, were summarized.And, reported anti-cancer mechanisms of cardenolides, structure analogues of bufadienolides, were also introduced. Based on the results got from research of Chan Su/bufalin and the results from cardenolides, possible signal network related to the anti-cancer effects of Chan Su/bufalin was predicted. Furthermore, future potential use of Chan Su in anti-cancer therapy was discussed.展开更多
Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is...Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.展开更多
Aging is an unavoidable topic in everyone's life, and the aging problem has been puzzling scientists for many years. For thousands of years, we've used many tools to extend life span, and today, new technologi...Aging is an unavoidable topic in everyone's life, and the aging problem has been puzzling scientists for many years. For thousands of years, we've used many tools to extend life span, and today, new technologies and medical treatments have extended the average human lifespan by about two years in a decade. The incidence of heart disease, tumors and degenerative diseases increases with age. Traditional Chinese Medicine believes that the use of herbs or guidance techniques can improve blood circulation, increase heart function, delay aging and prevent the development of tumors. Cardiac glycosides (CGS) are glycoside compounds that stimulate cardiac muscle significantly.展开更多
BACKGROUND At present,colorectal cancer is routinely treated with adjuvant radiotherapy and chemotherapy postoperatively.The adverse effects(AEs)of chemotherapy usually interrupt the treatment of chemotherapy.Traditio...BACKGROUND At present,colorectal cancer is routinely treated with adjuvant radiotherapy and chemotherapy postoperatively.The adverse effects(AEs)of chemotherapy usually interrupt the treatment of chemotherapy.Traditional Chinese medicine(TCM)has demonstrated great potential in improving patients'clinical symptoms,regulating the immune function,improving the life quality,and reducing the AEs of chemotherapy.AIM To observe the clinical efficacy of Yiqi Jianpi anti-cancer prescription combined with chemotherapy in patients with colorectal cancer after operation.METHODS Data from patients diagnosed with colorectal cancer between January 2019 and February 2021 were collected from Liaoning Cancer Hospital and Institute and the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine.Patients receiving the chemotherapy regimen of capecitabine plus oxaliplatin(CAPOX)after radical resection of colorectal cancer were prospectively collected and randomly divided into an experimental group and a control group.The experimental group was given Yiqi Jianpi anti-cancer prescription combined with the CAPOX regimen,while the control group was given the CAPOX regimen alone.After six cycles of chemotherapy,the scores of TCM symptoms,Karnofsky performance scale(KPS)score,levels of T-cell subsets,and AEs after chemo therapy of the two groups were compared.RESULTS A total of 70 patients were randomly divided into either an experimental group(n=35,no dropout)or a control group(n=33,with 2 dropouts).Compared with the control group,the experimental group improved significantly(P<0.05)in scores of TCM symptoms,KPS score,levels of T-cell subsets,and AEs of chemotherapy.CONCLUSION Yiqi Jianpi anti-cancer prescription can effectively improve spleen deficiency,regulate the immune function,and alleviate the AEs of chemotherapy,so as to improve the life quality of patients with good therapeutic effects and application prospect in clinical practice.展开更多
Objective: To study the isolated from the essential oil VIVO anti-tumor activities of furanodiene of the rhizome of Curcuma wenyujin (C15H200), a primary sesquiterpene compound YH Chen et C. Ling(Wen Ezhu), in vi...Objective: To study the isolated from the essential oil VIVO anti-tumor activities of furanodiene of the rhizome of Curcuma wenyujin (C15H200), a primary sesquiterpene compound YH Chen et C. Ling(Wen Ezhu), in vitro and in Methods: In vitro MTT assay was used to further study the effects of time and dosage on anti-proliferation of furanodiene against the sensitive Hela, Hep-2, HL-60, U251 cells, based on the cytotoxic effects of furanodiene on 12 human malignant tumor cell lines with the essential oil of Wen Ezhn as control., and the half-inhibitory concentration (IC50) was observed. In vivo uterine cervix (U14) tumor cell was selected and the conventional assay method of anti-tumor activity was employed. Furanodiene liposome was administered intraperitoneally, and tumor-inhibitory rate, thymus and spleen indexes were observed. Results: The inhibitive effects on cell proliferation were shown in all of the twelve cell lines and the cytotoxic effects of furanodiene against Hela, Hep-2, HL-60, U251 cells were observed after 12 h of administration, the effect could last for at least 48 h in a dose dependent manner, and the IC50 values were 0.6, 1.7, 1.8, 7.0μg/ml, respectively. Furanodiene was also found to show inhibitive effects on the proliferation of uterine cervix (U14) tumor induced in mice. The tumor inhibition rates were 36.09% (40 mg/kg), 41.55% (60 mg/kg), 58.29% (80 mg/kg), respectively. Conclusion: Furanodiene is one of primary anti-cancer active components in the essential oil of Wen Ezhu, and also a very effective agent against uterine cervix cancer, and has protection effect on the immune function.展开更多
A series of ruthenium azopyridine complexes have recently been investigated due to their potential cytotoxic activities against renal cancer (A498), lung cancer (H226), ovarian cancer (IGROV), breast cancer (MCF-7) an...A series of ruthenium azopyridine complexes have recently been investigated due to their potential cytotoxic activities against renal cancer (A498), lung cancer (H226), ovarian cancer (IGROV), breast cancer (MCF-7) and colon cancer (WIDR). Thus, in order to predict the cytotoxic potentials of these compounds, quantitative structure-activity relationship studies were carried out using the methods of quantum chemistry. Five Quantitative Structure Activity Relationship (QSAR) models were obtained from the determined quantum descriptors and the different activities. The models present the following statistical indicators: regression correlation coefficient R2 = 0.986 - 0.905, standard deviation S = 0.516 - 0.153, Fischer test F = 106.718 - 14.220, correlation coefficient of cross-validation = 0.985- 0.895 and = 0.010 - 0.001. The statistical characteristics of the established QSAR models satisfy the acceptance and external validation criteria, thereby accrediting their good performance. The models developed show that the variation of the free enthalpy of reaction , the dipole moment μ and the charge of the ligand in the complex Ql, are the explanatory and predictive quantum descriptors correlated with the values of the anti-cancer activity of the studied complexes. Moreover, the charge of the ligand is the priority descriptor for the prediction of the cytotoxicity of the compounds studied. Furthermore, QSAR models developed are statistically significant and predictive, and could be used for the design and synthesis of new anti-cancer molecules.展开更多
BACKGROUND Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma(PDAC)in order to improve their chances of survival.Recent studies have shown potent...BACKGROUND Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma(PDAC)in order to improve their chances of survival.Recent studies have shown potent anti-neoplastic effects of curcumin and its analogues.In addition,the role of histone methyltransferases on cancer therapeutics has also been elucidated.However,the relationship between these two factors in the treatment of pancreatic cancer remains unknown.Our working hypothesis was that L48H37,a novel curcumin analog,has better efficacy in pancreatic cancer cell growth inhibition in the absence of histonelysine N-methyltransferase 2D(KMT2D).AIM To determine the anti-cancer effects of L48H37 in PDAC,and the role of KMT2D on its therapeutic efficacy.METHODS The viability and proliferation of primary(PANC-1 and MIA PaCa-2)and metastatic(SW1990 and ASPC-1)PDAC cell lines treated with L48H37 was determined by CCK8 and colony formation assay.Apoptosis,mitochondrial membrane potential(MMP),reactive oxygen species(ROS)levels,and cell cycle profile were determined by staining the cells with Annexin-V/7-AAD,JC-1,DCFH-DA,and PI respectively,as well as flow cytometric acquisition.In vitro migration was assessed by the wound healing assay.The protein and mRNA levels of relevant factors were analyzed using Western blotting,immunofluorescence and real time-quantitative PCR.The in situ expression of KMT2D in both human PDAC and paired adjacent normal tissues was determined by immunohistochemistry.In vivo tumor xenografts were established by injecting nude mice with PDAC cells.Bioinformatics analyses were also conducted using gene expression databases and TCGA.RESULTS L48H37 inhibited the proliferation and induced apoptosis in SW1990 and ASPC-1 cells in a dose-and time-dependent manner,while also reducing MMP,increasing ROS levels,arresting cell cycle at the G2/M stages and activating the endoplasmic reticulum(ER)stress-associated protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4(ATF4)/CHOP signaling pathway.Knocking down ATF4 significantly upregulated KMT2D in PDAC cells,and also decreased L48H37-induced apoptosis.Furthermore,silencing KMT2D in L48H37-treated cells significantly augmented apoptosis and the ER stress pathway,indicating that KMT2D depletion is essential for the anti-neoplastic effects of L48H37.Administering L48H37 to mice bearing tumors derived from control or KMT2Dknockdown PDAC cells significantly decreased the tumor burden.We also identified several differentially expressed genes in PDAC cell lines expressing very low levels of KMT2D that were functionally categorized into the extrinsic apoptotic signaling pathway.The KMT2D high-and low-expressing PDAC patients from the TCGA database showed similar survival rates,but higher KMT2D expression was associated with poor tumor grade in clinical and pathological analyses.CONCLUSION L48H37 exerts a potent anti-cancer effect in PDAC,which is augmented by KMT2D deficiency.展开更多
Objective:To investigate the biochemical constituents of the fruits of Terminalia bellerica(Gaertn.)Roxb.(hereafter termed T.bellerica)and estimate the anti-cancer activity of different polar extracts.Methods:To rapid...Objective:To investigate the biochemical constituents of the fruits of Terminalia bellerica(Gaertn.)Roxb.(hereafter termed T.bellerica)and estimate the anti-cancer activity of different polar extracts.Methods:To rapidly screen and identify the biochemical constituents of ethyl acetate(EA)extracts of T.bellerica,ultra performance liquid chromatography-electrospray ionization/mass spectrometry(UPLC-ESI-MSn)was done.The CellTiter-BlueTM cell-viability assay was used to ascertain the anti-cancer activity of different polar extracts in 10 human cancer cell lines.Results:Forty polyphenols of the EA extract of T.bellerica were characterized tentatively.The EA extract exhibited significant anti-cancer activity against ZR-75-1 cells(half-maximal inhibitory concentration=27.33(0.98)μg/mL)and Colo-205 cells(39.65(2.99)μg/mL)in vitro.Treatment of ZR-75-1 cells with 20 and 60μg/mL of the EA extract elicited dosedependent apoptosis percentages at an early stage of 17.58(0.74)%and at a late stage of 29.20(1.22)%;Colo-205 cells at the same concentration of EA extract had values of 21.33(1.03)%and 40.55(0.34)%,respectively.Western blotting suggested that ZR-75-1 and Colo205 cells treated with the EA extract showed a similar increasing tendency for expression of cleaved anti-poly adenosine diphosphate ribose polymerase I.Conclusion:We identified a total of 40 chemical constituents,of which 11 were first obtained from the Terminalia Linn.genus using UPLC-ESI-MSn.Meanwhile,we observe that the EA extract of T.bellerica possesses anti-cancer activity,especially against breast and colon cancers.展开更多
Objective:To evaluate the potential immunomodulatory effects of an aqueous extract of Sesamum indicum seeds with regard to splenocyte proliferation,Th1/Th2 balance,macrophage function,and the cytotoxic activity of nat...Objective:To evaluate the potential immunomodulatory effects of an aqueous extract of Sesamum indicum seeds with regard to splenocyte proliferation,Th1/Th2 balance,macrophage function,and the cytotoxic activity of natural killer(NK)cells.Methods:Splenocyte proliferation was measured by[~3H]-thymidine incorporation.Griess assay was performed to evaluate the production of nitric oxide by macrophages.The levels of cytokines secreted by splenocytes and macrophages were measured by ELISA.JAM assay was performed to examine the cytotoxic activity of NK cells against YAC-1 tumor cells.Results:Sesamum indicum significantly enhanced splenocyte proliferation in a dose-dependent manner.Sesamum indicum also increased and suppressed the secretion of Th1 and Th2 cytokines,respectively,by splenocytes.The secretion of key pro-inflammatory mediators(IL-6,TNFα,and nitric oxide)by primary macrophages was significantly inhibited by Sesamum indicum.Moreover,Sesamum indicum increased the cytotoxic activity of NK cells against YAC-1 tumor cells.Conclusions:Sesamum indicum shows potent immunomodulatory,anti-inflammatory,and anti-cancer effects.Constituents of Sesamum indicum may be used as effective therapeutic agents in regulating immune reactions implicated in various infectious and noninfectious conditions including cancer.展开更多
Objective:To explore antioxidant potential,anti-cancer activity,and phytochemicals of Commelina benghalensis L.Methods:The roots of Commelina benghalensis were extracted in different solvents(methanol,ethanol,benzene,...Objective:To explore antioxidant potential,anti-cancer activity,and phytochemicals of Commelina benghalensis L.Methods:The roots of Commelina benghalensis were extracted in different solvents(methanol,ethanol,benzene,chloroform,n-hexane)with a range of polarity.Antioxidant activity was evaluated by reducing power assay,DPPH radical scavenging activity and phosphomolybdenum method,cytotoxicity by MTT assay,apoptotic and cell cycle analysis by flow cytometry,migratory and invasive potential by wound scratch assay and invasion assay,respectively,functional groups analysis by FT-IR spectroscopy and phytochemicals by aluminum chloride colorimetric and FolinCiocalteu methods.Results:The extracts showed worthy antioxidant potential.The chloroform extract demonstrated the most significant cytotoxic effect on MDA-MB-231(breast cancer)cell line,induced apoptosis and reduced migratory and invasive potential of MDA-MB-231 cells.Methanol and ethanol extracts presented good yield of total phenolic and total flavonoid contents.The FTIR spectroscopic studies revealed different characteristic peak values with various functional compounds such as alkenes,alkanes,aliphatic amines,aromatics,alkyl halides,carboxylic acid,alcohols,ester,aldehydes and ketones.Conclusions:The results demonstrate the potential use of Commelina benghalensis as a good antioxidant with significant anticancer effect.展开更多
Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-...Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-itrile as the mobile phase at a flow rate of 1.0 mL/min. The detecting wavelength was set at 210 nm, and the column temperature was set at 30℃. Result: in the method validation, the linear relationship modulus of picoplatin is 0.9999, the systemic precision is 0.44%, the method precision is 0.74%, the average recovery rate is 99.62%, the LOD and LOQ of picoplatin is 0.2 ng and 1.0 ng. The average resolution of picoplatin and its impurities is more than 2. Conclusion: The established method is good specificity, high sensitivity, and good repeatability which could provide scientific evidence for the quality control of picoplatin and its impurities.展开更多
基金Supported by a grant from the Natural Science Foundation of Liaoning Province(No.201202043)
文摘Objective: The aim of our study was to explore the inhibition and apoptosis-inducing effect of the combination of Huaier aqueous extract with recombinant human Endostatin and DDP in human lung adenocarcinoma A549 cells. We also investigated the reversal effect of Huaier aqueous extract in reversing cisplatin resistance in human lung adenocarcinoma A549/DDP cells. Methods: We treated A549 cells with Huaier aqueous extract and the combination of Huaier aqueous extract and DDP or rh-Endostatin for 24 h, 36 h and 48 h. And then we calculated the inhibition rate through MTT approach and detected the apoptosis rate by flow cytometry. We also treated A549 and A549/DDP cells with DDP, Huaier aqueous extract, DDP and Huaier aqueous extract for 72 h, respectively. Results: Huaier aqueous extract can inhibit the growth of A549 cells and the inhibition rate improved with the increase of the concentration. The inhibition rate of the combination of rh-Endostatin and 4 mg/mL of Huaier aqueous extract in three time points and the combination of rh-Endostatin and 2 mg/mL of Huaier aqueous extract in the time point of 48 h on the growth of A549 cells all improved(P < 0.005). The inhibition rate of the combination of DDP and Huaier aqueous extract with the concentration of 2 mg/mL or 4 mg/mL on the growth of A549 cells all improved(P < 0.005). The combination of Huaier aqueous extract and DDP and the combination of Huaier aqueous extract with rh-Endostatin and DDP can improve the inhibition on the growth of A549 cells(P < 0.005). Conclusion: Huaier aqueous extract has the inhibition and apoptosis-inducing effects on the A549 cells. And the combination of Huaier aqueous extract and rh-Endostatin or DDP has the synergistic effects on the inhibition of A549 cells. The combination of Huaier aqueous extract with rh-Endostatin and DDP has the synergistic effects on the inhibition of A549 cells. Huaier aqueous extract can reverse the cisplatin resistance in human lung adenocarcinoma A549/DDP cells.
文摘After more than a decade of controversy on the role of stromal cells in the tumor microenvironment,the emerging data shed light on pro-tumorigenic and potential anti-cancer factors,as well as on the roots of the discrepancies.We discuss the pro-tumorigenic effects of stromal cells,considering the effects of tumor drivers like hypoxia and tumor stiffness on these cells,as well as stromal cell-mediated adiposity and immunosuppression in the tumor microenvironment,and cancer initiating cells'cellular senescence and adaptive metabolism.We summarize the emerging data supporting stromal cell therapeutic potential in cancer,discuss the possibility to reprogram stromal cells of the tumor microenvironment for anti-cancer effects,and explore some causes of discrepancies on the roles of stromal cells in cancer in the available literature.
基金supported by the 2016 Inje University research grant
文摘Objective: To investigate the anti-colon cancer effects of ethylacetate fraction from Orostachys japonicus(0. japonicus) on HT-29 cancer cells. Methods: The viability of HT-29 cells was assayed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium(MTS) method. Apoptosis induction and cell cycle inhibition were confirmed by fluorescein isothiocyanate and propidium iodide staining using flow cytometry.Morphological changes in the nucleus were observed, using a fluorescence microscope with4',6-diamidino-2-phenylindole(DAPI) nuclear staining. The expression levels of the upstream and downstream proteins involved in the anti-cancer mechanism were confirmed by Western blotting. Results: After treating HT-29 cells with different concentrations of ethylacetate fraction from O. japonicus, the viability of cells decreased in a concentration-dependent manner,while apoptosis induction and apoptotic body formation increased. Cell cycle analysis showed that the arrest occurred at the sub-G_1 and S phase. Among the upstream and downstream proteins involved in anti-cancer activity, the level of B cell lymphoma-2 decreased, and the bcl-2-associated x protein increased. The level of pro-caspase-3, pro-caspase-8, and pro-caspase-9 decreased, while the level of cleaved-caspase-3, cleaved-caspase-8, and cleaved-caspase-9 increased. Moreover, the phosphorylation, that is, activation of extracellular signal regulated kinase 1/2, Jun-N-terminal kinase, and p38 increased. Conclusions: Combining the above results, it is thought that the survival of HT-29 cells is suppressed by ethylacetate fraction from0. japonicus through mitochondrial regulation-induced caspase cascade activation, induction of apoptosis and cell cycle arrest.
基金Supported by the Natural Science Foundation of Capital Medical University,No.PYZ20014 and No.PYZ21074。
文摘BACKGROUND Glycolysis caused by hypoxia-induced abnormal activation of hypoxia inducible factor-1α(HIF-1α)in the immune microenvironment promotes the progression of hepatocellular carcinoma(HCC),leading to enhanced drug resistance in cancer cells.Therefore,altering the immunosuppressive microenvironment by improving the hypoxic state is a new goal in improving cancer treatment.AIM To analyse the role of HIF-1α,which is closely related to tumour proliferation,invasion,metastasis,and angiogenesis,in the proliferation and invasion of liver cancer,and to explore the HIF-1αpathway-mediated anti-cancer mechanism of sirolimus(SRL)combined with Huai Er.METHODS Previous studies on HCC tissues identified the importance of HIF-1α,glucose transporter 1(GLUT1),and lactate dehydrogenase A(LDHA)expression.In this study,HepG2 and Huh7 cell lines were treated,under hypoxic and normoxic conditions,with a combination of SRL and Huai Er.The effects on proliferation,invasion,cell cycle,and apoptosis were analysed.Proteomics and genomics techniques were used to analyze the HIF-1α-related signalling pathway during SRL combined with Huai Er treatment and its inhibition of the proliferation of HCC cells.RESULTS High levels of HIF-1α,LDHA,and GLUT-1 were found in poorly differentiated HCC,with lower patient survival rates.Hypoxia promoted the proliferation of HepG2 and Huh7 cells and weakened the apoptosis and cell cycle blocking effects of the SRL/Huai Er treatment.This was achieved by activation of HIF-1αand glycolysis in HCC,leading to the upregulation of LDHA,GLUT-1,Akt/mammalian target of rapamycin(mTOR),vascular endothelial growth factor(VEGF),and Forkhead box P3 and downregulation of phosphatase and tensin homolog deleted on chromosome ten(PTEN)and p27.The hypoxia-induced activation of HIF-1αshowed the greatest attenuation in the SRL/Huai Er(S50+H8)group compared to the drug treatments alone(P<0.001).The S50+H8 treatment significantly downregulated the expression of mTOR and HIF-1α,and significantly reduced the expression of VEGF mRNA.Meanwhile,the combined blocking of mTOR and HIF-1αenhanced the downregulation of Akt/mTOR,HIF-1α,LDHA,and GLUT-1 mRNA and resulted in the downregulation of PTEN,p27,and VEGF mRNA(P<0.001).CONCLUSION SRL increases the anti-cancer effect of Huai Er,which reduces the promotion of hypoxia-induced HIF-1αon the Warburg effect by inhibition of the PI3K/Akt/mTOR-HIF-1αand HIF-1α-PTEN signalling pathways in HCC.
基金This study was supported by local special projects in major health of Hubei Provincial Science and Technology Department(2022BCE054)key scientific research projects of Hubei polytechnic University(23xjz08A).
文摘Taraxasterol(TS)is a naturally occurring pentacyclic triterpenoid extracted from the traditional Chinese herb Taraxacum mongolicum.Previous studies have highlighted its significant roles in exhibiting anti-inflammatory,anti-oxidant,and liver protective effects.In the present study,the anti-cancer potential of TS against cervical cancer was investigated,employing network pharmacology techniques,molecular docking,and in vitro experimental validation.TS exhibits its anticancer properties by modulating multiple targets,pathways,and biological processes.In vitro experiments demonstrated the potent inhibitory effects of TS on cancer cell growth and migration,while no significant impact on apoptosis was observed.The primary objective was to elucidate the anti-cancer potential of TS,which is a crucial lead compound in the treatment of cervical cancer.The findings may serve as a basis for the development of novel anticancer therapeutics and medicine-based interventions for cervical cancer.
基金Supported by Talent Training Project of Central Support for the Reform and Development Fund of Local Colleges and Universities(2020GSP16)Heilongjiang Provincial Key R&D Plan Guidance Project(GZ20220039)Daqing Guiding Science and Technology Project(zdy-2024-91).
文摘Rhodiola rosea,a perennial herb of the genus Rhodiola in the Crassulaceae family,is commonly used to treat depression,fatigue,cancer and cardiovascular diseases.Herbacetin is a natural flavonol compound extracted from R.rosea plant,with many pharmacological effects such as anti-cancer effect,anti-oxidant effect and anti-inflammatory effect.In this paper,the pharmacological effects and molecular mechanisms of herbacetin were summarized by consulting domestic and foreign literature,in order to provide a theoretical basis for the development and utilization of herbacetin.
文摘Polysocoharibe-peptide of Coriolus Versicolor (PSP) is a new anti-cancer immunomodulative drug. The present paper reports on the experimental research done with this drug. It was found that PSP had the ability to recover hemolysin HC50, to increase the weight of the thymus, and increase the alexin of serum C3 and the IgG content of tumor bearing mice. FSP also significantly raised the pha-gocytic activity of macrophages in normal mice. PSP had a significant inhibitory effect on P38S and S180 cells. At the concentration of 1 mg/ml, PSP inhibited the proliferating activity of some human tumor call lines, such as SGC 7901, SPC, SLY and Mei. It had a direct toxic effect on SPC cells. PSP significantly inhibited the synthesis of nucleic acids of Ehrlich ascites carcinoma cells. In addition, PSP was antagonistic to the side effects of chemotherapy and radiotherapy.
基金supported by a grant of the French-Thai cooperation PHC SIAM 2011(project 25587RA).
文摘Medicinal mushrooms have been valued as natural sources of bioactive compounds since times immemorial and have been recognized as potential immunomodulating and anti-cancer agents.Their consumption has consistently been shown to have beneficial effects on human health.Cancer is a generic term for several types of diseases that can be chronic and are responsible for a large number of deaths worldwide.Although there has been considerable progress in modern cancer therapy research,difficulties in understanding the molecular behavior of various types of cancers and the numerous side effects experienced by patients from treatments means that this whole subject area is still problematic.Thus,biological immunotherapy using natural bioactive compounds as supportive treatments in conventional cancer therapies has become in vogue.Bioactive metabolites isolated from medicinal mushrooms have shown potential successes in cancer treatment as biological immunotherapeutic agents that stimulate the immune system against cancer cells.They also act as an effective source of anti-cancer agents,capable of interfering with cellular signal transduction pathways linked to cancer development and progression.In this review we compile available data on the characteristics of medicinal mushrooms that appear to be particularly effective as biological immunotherapeutic agents.Major consideration is given to biological constituents and the putative mechanisms of action by which bioactive compounds act on the human body.Consideration is also given to the benefits that have been claimed for the use of mushrooms in treating cancer and the future prospects of using medicinal mushrooms as potent supportive candidate bioagents for treatment of cancers is discussed.
文摘Objective: There were some experimental researches in vitro, which showed that tanshinonoe (Tan) had cytotoxic activities against some cancer cell lines. But there was no report of anticancer activity of Tan in vivo. This experimental study was performed to confirm the anticancer activity of Tan in vivo. Methods: Hepatic carcinoma H22 bearing mice were treated with DMSO, 5Fu, and Tan, at the end of experiment, the mice were sacrificed, tumor tissues were separated and weighed, and the tumor inhibitory rate was calculated, 3 times of the same experiments were performed. The proliferating kinetics of hepatic carcinoma H22 cells in mice was measured by bromodeoxyuridine labeling in vivo and immunohistochemical staining of the proliferating cell nuclear antigen (PCNA) in tumor tissues. Results: The tumor inhibitory rates of Tan were 50.0%, 38.5%, and 40.6% in 3 experiments, respectively, compared with those of the DMSOtreated control groups, the differences were significant statistically (P<0.01). The Brdu labeling and PCNA positive cells were 51.8±7.9 and 451.1±26.1, respectively, which were significantly lower than those of controls (84.4±24.3, 694.8±117.1) (P<0.01). Conclusion: Tan had anticancer effect on hepatic carcinoma in vivo; The mechanisms of action might be associated with inhibition of DNA synthesis, PCNA expression and DNA polymerase δ activity of tumor cells.
基金Partly supported by the National Science&technology Major Project of China(2014ZX09301-306-03)Shanghai Science&Technology Support Program(13431900401)the National Nature Science Foundation of China(81373964)
文摘Toad venom, called as Chan Su in China, is a widely used traditional Chinese medicine(TCM) whose active components are mainly bufadienolides. Chan Su could exhibit cardiotonic, anti-microbial, anti-inflammatory and, most importantly, anti-cancer effects. In the present review, reports about the in vitro, in vivo and clinical anti-cancer effects of Chan Su or its representative component, bufalin, were summarized.And, reported anti-cancer mechanisms of cardenolides, structure analogues of bufadienolides, were also introduced. Based on the results got from research of Chan Su/bufalin and the results from cardenolides, possible signal network related to the anti-cancer effects of Chan Su/bufalin was predicted. Furthermore, future potential use of Chan Su in anti-cancer therapy was discussed.
文摘Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.
文摘Aging is an unavoidable topic in everyone's life, and the aging problem has been puzzling scientists for many years. For thousands of years, we've used many tools to extend life span, and today, new technologies and medical treatments have extended the average human lifespan by about two years in a decade. The incidence of heart disease, tumors and degenerative diseases increases with age. Traditional Chinese Medicine believes that the use of herbs or guidance techniques can improve blood circulation, increase heart function, delay aging and prevent the development of tumors. Cardiac glycosides (CGS) are glycoside compounds that stimulate cardiac muscle significantly.
文摘BACKGROUND At present,colorectal cancer is routinely treated with adjuvant radiotherapy and chemotherapy postoperatively.The adverse effects(AEs)of chemotherapy usually interrupt the treatment of chemotherapy.Traditional Chinese medicine(TCM)has demonstrated great potential in improving patients'clinical symptoms,regulating the immune function,improving the life quality,and reducing the AEs of chemotherapy.AIM To observe the clinical efficacy of Yiqi Jianpi anti-cancer prescription combined with chemotherapy in patients with colorectal cancer after operation.METHODS Data from patients diagnosed with colorectal cancer between January 2019 and February 2021 were collected from Liaoning Cancer Hospital and Institute and the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine.Patients receiving the chemotherapy regimen of capecitabine plus oxaliplatin(CAPOX)after radical resection of colorectal cancer were prospectively collected and randomly divided into an experimental group and a control group.The experimental group was given Yiqi Jianpi anti-cancer prescription combined with the CAPOX regimen,while the control group was given the CAPOX regimen alone.After six cycles of chemotherapy,the scores of TCM symptoms,Karnofsky performance scale(KPS)score,levels of T-cell subsets,and AEs after chemo therapy of the two groups were compared.RESULTS A total of 70 patients were randomly divided into either an experimental group(n=35,no dropout)or a control group(n=33,with 2 dropouts).Compared with the control group,the experimental group improved significantly(P<0.05)in scores of TCM symptoms,KPS score,levels of T-cell subsets,and AEs of chemotherapy.CONCLUSION Yiqi Jianpi anti-cancer prescription can effectively improve spleen deficiency,regulate the immune function,and alleviate the AEs of chemotherapy,so as to improve the life quality of patients with good therapeutic effects and application prospect in clinical practice.
基金supported by the Natural Science Foundation of Shandong Province of China (No Y2008C67)the Sci & Tech Development Plan Project of Shandong Provincial Education Department (No J07W01)
文摘Objective: To study the isolated from the essential oil VIVO anti-tumor activities of furanodiene of the rhizome of Curcuma wenyujin (C15H200), a primary sesquiterpene compound YH Chen et C. Ling(Wen Ezhu), in vitro and in Methods: In vitro MTT assay was used to further study the effects of time and dosage on anti-proliferation of furanodiene against the sensitive Hela, Hep-2, HL-60, U251 cells, based on the cytotoxic effects of furanodiene on 12 human malignant tumor cell lines with the essential oil of Wen Ezhn as control., and the half-inhibitory concentration (IC50) was observed. In vivo uterine cervix (U14) tumor cell was selected and the conventional assay method of anti-tumor activity was employed. Furanodiene liposome was administered intraperitoneally, and tumor-inhibitory rate, thymus and spleen indexes were observed. Results: The inhibitive effects on cell proliferation were shown in all of the twelve cell lines and the cytotoxic effects of furanodiene against Hela, Hep-2, HL-60, U251 cells were observed after 12 h of administration, the effect could last for at least 48 h in a dose dependent manner, and the IC50 values were 0.6, 1.7, 1.8, 7.0μg/ml, respectively. Furanodiene was also found to show inhibitive effects on the proliferation of uterine cervix (U14) tumor induced in mice. The tumor inhibition rates were 36.09% (40 mg/kg), 41.55% (60 mg/kg), 58.29% (80 mg/kg), respectively. Conclusion: Furanodiene is one of primary anti-cancer active components in the essential oil of Wen Ezhu, and also a very effective agent against uterine cervix cancer, and has protection effect on the immune function.
文摘A series of ruthenium azopyridine complexes have recently been investigated due to their potential cytotoxic activities against renal cancer (A498), lung cancer (H226), ovarian cancer (IGROV), breast cancer (MCF-7) and colon cancer (WIDR). Thus, in order to predict the cytotoxic potentials of these compounds, quantitative structure-activity relationship studies were carried out using the methods of quantum chemistry. Five Quantitative Structure Activity Relationship (QSAR) models were obtained from the determined quantum descriptors and the different activities. The models present the following statistical indicators: regression correlation coefficient R2 = 0.986 - 0.905, standard deviation S = 0.516 - 0.153, Fischer test F = 106.718 - 14.220, correlation coefficient of cross-validation = 0.985- 0.895 and = 0.010 - 0.001. The statistical characteristics of the established QSAR models satisfy the acceptance and external validation criteria, thereby accrediting their good performance. The models developed show that the variation of the free enthalpy of reaction , the dipole moment μ and the charge of the ligand in the complex Ql, are the explanatory and predictive quantum descriptors correlated with the values of the anti-cancer activity of the studied complexes. Moreover, the charge of the ligand is the priority descriptor for the prediction of the cytotoxicity of the compounds studied. Furthermore, QSAR models developed are statistically significant and predictive, and could be used for the design and synthesis of new anti-cancer molecules.
文摘BACKGROUND Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma(PDAC)in order to improve their chances of survival.Recent studies have shown potent anti-neoplastic effects of curcumin and its analogues.In addition,the role of histone methyltransferases on cancer therapeutics has also been elucidated.However,the relationship between these two factors in the treatment of pancreatic cancer remains unknown.Our working hypothesis was that L48H37,a novel curcumin analog,has better efficacy in pancreatic cancer cell growth inhibition in the absence of histonelysine N-methyltransferase 2D(KMT2D).AIM To determine the anti-cancer effects of L48H37 in PDAC,and the role of KMT2D on its therapeutic efficacy.METHODS The viability and proliferation of primary(PANC-1 and MIA PaCa-2)and metastatic(SW1990 and ASPC-1)PDAC cell lines treated with L48H37 was determined by CCK8 and colony formation assay.Apoptosis,mitochondrial membrane potential(MMP),reactive oxygen species(ROS)levels,and cell cycle profile were determined by staining the cells with Annexin-V/7-AAD,JC-1,DCFH-DA,and PI respectively,as well as flow cytometric acquisition.In vitro migration was assessed by the wound healing assay.The protein and mRNA levels of relevant factors were analyzed using Western blotting,immunofluorescence and real time-quantitative PCR.The in situ expression of KMT2D in both human PDAC and paired adjacent normal tissues was determined by immunohistochemistry.In vivo tumor xenografts were established by injecting nude mice with PDAC cells.Bioinformatics analyses were also conducted using gene expression databases and TCGA.RESULTS L48H37 inhibited the proliferation and induced apoptosis in SW1990 and ASPC-1 cells in a dose-and time-dependent manner,while also reducing MMP,increasing ROS levels,arresting cell cycle at the G2/M stages and activating the endoplasmic reticulum(ER)stress-associated protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4(ATF4)/CHOP signaling pathway.Knocking down ATF4 significantly upregulated KMT2D in PDAC cells,and also decreased L48H37-induced apoptosis.Furthermore,silencing KMT2D in L48H37-treated cells significantly augmented apoptosis and the ER stress pathway,indicating that KMT2D depletion is essential for the anti-neoplastic effects of L48H37.Administering L48H37 to mice bearing tumors derived from control or KMT2Dknockdown PDAC cells significantly decreased the tumor burden.We also identified several differentially expressed genes in PDAC cell lines expressing very low levels of KMT2D that were functionally categorized into the extrinsic apoptotic signaling pathway.The KMT2D high-and low-expressing PDAC patients from the TCGA database showed similar survival rates,but higher KMT2D expression was associated with poor tumor grade in clinical and pathological analyses.CONCLUSION L48H37 exerts a potent anti-cancer effect in PDAC,which is augmented by KMT2D deficiency.
基金supported by the National Natural Science Foundation of China:Surface Project(81274187)Longitudinal Research Project of the Beijing University of Chinese Medicine(2020072120043).
文摘Objective:To investigate the biochemical constituents of the fruits of Terminalia bellerica(Gaertn.)Roxb.(hereafter termed T.bellerica)and estimate the anti-cancer activity of different polar extracts.Methods:To rapidly screen and identify the biochemical constituents of ethyl acetate(EA)extracts of T.bellerica,ultra performance liquid chromatography-electrospray ionization/mass spectrometry(UPLC-ESI-MSn)was done.The CellTiter-BlueTM cell-viability assay was used to ascertain the anti-cancer activity of different polar extracts in 10 human cancer cell lines.Results:Forty polyphenols of the EA extract of T.bellerica were characterized tentatively.The EA extract exhibited significant anti-cancer activity against ZR-75-1 cells(half-maximal inhibitory concentration=27.33(0.98)μg/mL)and Colo-205 cells(39.65(2.99)μg/mL)in vitro.Treatment of ZR-75-1 cells with 20 and 60μg/mL of the EA extract elicited dosedependent apoptosis percentages at an early stage of 17.58(0.74)%and at a late stage of 29.20(1.22)%;Colo-205 cells at the same concentration of EA extract had values of 21.33(1.03)%and 40.55(0.34)%,respectively.Western blotting suggested that ZR-75-1 and Colo205 cells treated with the EA extract showed a similar increasing tendency for expression of cleaved anti-poly adenosine diphosphate ribose polymerase I.Conclusion:We identified a total of 40 chemical constituents,of which 11 were first obtained from the Terminalia Linn.genus using UPLC-ESI-MSn.Meanwhile,we observe that the EA extract of T.bellerica possesses anti-cancer activity,especially against breast and colon cancers.
文摘Objective:To evaluate the potential immunomodulatory effects of an aqueous extract of Sesamum indicum seeds with regard to splenocyte proliferation,Th1/Th2 balance,macrophage function,and the cytotoxic activity of natural killer(NK)cells.Methods:Splenocyte proliferation was measured by[~3H]-thymidine incorporation.Griess assay was performed to evaluate the production of nitric oxide by macrophages.The levels of cytokines secreted by splenocytes and macrophages were measured by ELISA.JAM assay was performed to examine the cytotoxic activity of NK cells against YAC-1 tumor cells.Results:Sesamum indicum significantly enhanced splenocyte proliferation in a dose-dependent manner.Sesamum indicum also increased and suppressed the secretion of Th1 and Th2 cytokines,respectively,by splenocytes.The secretion of key pro-inflammatory mediators(IL-6,TNFα,and nitric oxide)by primary macrophages was significantly inhibited by Sesamum indicum.Moreover,Sesamum indicum increased the cytotoxic activity of NK cells against YAC-1 tumor cells.Conclusions:Sesamum indicum shows potent immunomodulatory,anti-inflammatory,and anti-cancer effects.Constituents of Sesamum indicum may be used as effective therapeutic agents in regulating immune reactions implicated in various infectious and noninfectious conditions including cancer.
文摘Objective:To explore antioxidant potential,anti-cancer activity,and phytochemicals of Commelina benghalensis L.Methods:The roots of Commelina benghalensis were extracted in different solvents(methanol,ethanol,benzene,chloroform,n-hexane)with a range of polarity.Antioxidant activity was evaluated by reducing power assay,DPPH radical scavenging activity and phosphomolybdenum method,cytotoxicity by MTT assay,apoptotic and cell cycle analysis by flow cytometry,migratory and invasive potential by wound scratch assay and invasion assay,respectively,functional groups analysis by FT-IR spectroscopy and phytochemicals by aluminum chloride colorimetric and FolinCiocalteu methods.Results:The extracts showed worthy antioxidant potential.The chloroform extract demonstrated the most significant cytotoxic effect on MDA-MB-231(breast cancer)cell line,induced apoptosis and reduced migratory and invasive potential of MDA-MB-231 cells.Methanol and ethanol extracts presented good yield of total phenolic and total flavonoid contents.The FTIR spectroscopic studies revealed different characteristic peak values with various functional compounds such as alkenes,alkanes,aliphatic amines,aromatics,alkyl halides,carboxylic acid,alcohols,ester,aldehydes and ketones.Conclusions:The results demonstrate the potential use of Commelina benghalensis as a good antioxidant with significant anticancer effect.
文摘Purpose: To establish a HPLC testing method of the content of bulk picoplatin and its impurities. Method: the separation was perform on a C18 column(4.6 mm×250 mm, 5 m) with potassium dihydrogen phosphate-aceton-itrile as the mobile phase at a flow rate of 1.0 mL/min. The detecting wavelength was set at 210 nm, and the column temperature was set at 30℃. Result: in the method validation, the linear relationship modulus of picoplatin is 0.9999, the systemic precision is 0.44%, the method precision is 0.74%, the average recovery rate is 99.62%, the LOD and LOQ of picoplatin is 0.2 ng and 1.0 ng. The average resolution of picoplatin and its impurities is more than 2. Conclusion: The established method is good specificity, high sensitivity, and good repeatability which could provide scientific evidence for the quality control of picoplatin and its impurities.