In the present study,we introduced the H2O2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine(GEM)to synthesize a new target compound named GEM-ZZQ,and then we confirmed its chemical structure by n...In the present study,we introduced the H2O2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine(GEM)to synthesize a new target compound named GEM-ZZQ,and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy.We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could be activated by H2O2 to release GEM.Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM.For the lung cancer cell lines that are resistant to the epidermal growth factor receptor(EGFR)-targeting inhibitor osimertinib,GEM-ZZQ showed less growth inhibition than GEM;however,GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups.In summary,we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying the GEM structure.展开更多
Objective: To test the coalescence effect of two chemotherapy drugs at low effective dose(cisplatin and taxotere) combined with pomegranate juice on A549 cancer cells. Methods: Infrared spectroscopy method is a qualit...Objective: To test the coalescence effect of two chemotherapy drugs at low effective dose(cisplatin and taxotere) combined with pomegranate juice on A549 cancer cells. Methods: Infrared spectroscopy method is a qualitative test that was performed to ensure the existence of the phytochemicals providing the antioxidant activity through the presence of the hydroxyl group(-OH). The viability of A549 cell line and normal MCs was tested using the neutral red uptake, Clonogenic survival, XTT and Cell migration assays. Results: Our results showed that this combination firstly led to a greater decrease in the viability of cells comparing to those treated with chemotherapy drugs alone, and secondly led to a significant reduction in cell migration. Conclusions: These data suggest a synergistic effect between the pomegranate and cisplatin which makes probably this combination a powerful option for treating lung adenocarcinoma and in parallel minimizing the systemic side effects.展开更多
Alantolactone is a natural compound identified from the roots of Inula helenium L. that has multiple bio-activities. We examined its inhibitory effects on human non-small cell lung cancer（NSCLC） A549 cells. The an-t...Alantolactone is a natural compound identified from the roots of Inula helenium L. that has multiple bio-activities. We examined its inhibitory effects on human non-small cell lung cancer（NSCLC） A549 cells. The an-tiproliferative effect of alantolactone on A549 cells was investigated via MTT[3′-（4,5dimethylthiazol-2-yl）-2,5- diphenyl tetrazolium bromide] assay and its apoptosis-inducing effect was determined by Hoechst staining and flow cytometry. We found that alantolactone significantly inhibited the proliferation of A549 cells and induced morphological changes typical for apoptosis. Flow cytometry analysis indicates dose-dependent cell cycle retardation at G0/G1 and S stages. The results indicate that alantolactone could be an attractive small-molecular natural compound for further development as a therapeutic drug against NSCLC.展开更多
Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological pro...Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological properties of human lung carcinoma cells remain scarcely reported.Therefore,in the present study the magnetic c-Fe2O3nanoparticles(MNPs)were firstly synthesized and surface-modified with cationic poly-L-lysine(PLL)to construct the PLL-MNPs,which were then used to magnetically label human A549 lung cancer cells.Cell viability and proliferation were evaluated with propidium iodide/fluorescein diacetate double staining and standard 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium)bromide assay,and the cytoskeleton was immunocytochemically stained.The cell cycle of the PLL-MNPlabeled A549 lung cancer cells was analyzed using flow cytometry.Apoptotic cells were fluorescently analyzed with nuclear-specific staining after the PLL-MNP labeling.The results showed that the constructed PLL-MNPs efficiently magnetically labeled A549 lung cancer cells and that,at low concentrations,labeling did not affect cellular viability,proliferation capability,cell cycle,and apoptosis.Furthermore,the cytoskeleton in the treated cells was detected intact in comparison with the untreated counterparts.However,the results also showed that at high concentration(400 lg m L-1),the PLL-MNPs would slightly impair cell viability,proliferation,cell cycle,and apoptosis and disrupt the cytoskeleton in the treated A549 lung cancer cells.Therefore,the present results indicated that the PLL-MNPs at adequate concentrations can be efficiently used for labeling A549 lung cancer cells and could be considered as a feasible approach for magnetic targeted anti-cancer drug/gene delivery,targeted diagnosis,and therapy in lung cancer treatment.展开更多
Objective Loss-of-function mutation of p53,a tumor suppressor gene,is an important mechanism for the development of human cancers. In this study we tried to transfect p53N15-based fusion peptide into H1299,a lung canc...Objective Loss-of-function mutation of p53,a tumor suppressor gene,is an important mechanism for the development of human cancers. In this study we tried to transfect p53N15-based fusion peptide into H1299,a lung cancer cell line,and evaluate the anti-tumor effects of the fusion peptide. Methods Adeno-associated virus (AAV) vectors were used for transfecting p53N15 fusion peptide into p53-null lung adenocarcinoma H1299 cells.展开更多
Objective： To study the inhibition of Cantharidin against the proliferation of human lung cancer A549 cells and its mechanism. Methods： MTT assay was employed to determine the inhibition of Cantharidin against proli...Objective： To study the inhibition of Cantharidin against the proliferation of human lung cancer A549 cells and its mechanism. Methods： MTT assay was employed to determine the inhibition of Cantharidin against proliferation of A549 cells and flow Cytometry was applied to analyze A549 cell cycle and the effect of Cantharidin on cell cycle. Results： Cantharidin showed inhibition against the proliferation of A549 cells, and the inhibition was mediated by blocking A549 cell cycle at G2/M phase significantly. Conclusion： Cantharidin exhibits inhibition against the proliferation of human lung cancer A549 cells.展开更多
BACKGROUND The most common EGFR mutations are in-frame deletions in exon 19 and point mutations in exon 21.Cases with classical EGFR mutations show a good response to EGFR tyrosine kinase inhibitors(TKIs),the standard...BACKGROUND The most common EGFR mutations are in-frame deletions in exon 19 and point mutations in exon 21.Cases with classical EGFR mutations show a good response to EGFR tyrosine kinase inhibitors(TKIs),the standard first-line treatment.With the development of next generation sequencing,some uncommon genomic mutations have been detected.However,the effect of TKIs on such uncommon EGFR mutations remains unclear.CASE SUMMARY Here,we report a case of rare EGFR co-mutation in non-small cell lung cancer and the efficacy of afatinib on this EGFR co-mutation.A 64-year-old woman was diagnosed with thoracolumbar and bilateral local rib bone metastases,bilateral pulmonary nodules,and pericardial and left pleural effusion.The pathological diagnosis was lung adenocarcinoma.To seek potential therapeutic regimens,rare co-mutation comprising rare EGFR G724S/R776H mutations and amplification were identified.The patient experienced a significant clinical response with a progression-free survival of 17 mo.CONCLUSION A case of non-small cell lung cancer with rare EGFR G724S/R776H mutations and EGFR amplification responds well to TKI treatment.展开更多
Objective To observe the effect of Fuzheng Kang’ai Recipe(FKR)combined with gefitinib on the proliferation and apoptosis of lung cancer A549 cells,and to study its potential synergistic mechanish with gefitinib.Metho...Objective To observe the effect of Fuzheng Kang’ai Recipe(FKR)combined with gefitinib on the proliferation and apoptosis of lung cancer A549 cells,and to study its potential synergistic mechanish with gefitinib.Methods The effects of FKR(0.211,0.316,0.474,0.711,1.067,1.600,2.400,3.600 mg/mL)combined with展开更多
Beta catenin has been well documented in previous studies to be involved in non small cell lung cancer(NSCLC).Beta catenin abundance and transcriptional activity are significantly regulated by several factors.Though i...Beta catenin has been well documented in previous studies to be involved in non small cell lung cancer(NSCLC).Beta catenin abundance and transcriptional activity are significantly regulated by several factors.Though it is well known that Akt and Gsk3 beta are respective positive and negative regulators of beta catenin,however,no single study has so far documented how the expression and activity of both positive as well as negative regulators play favorable role on beta catenin expression and activity in NSCLC.In this study,we compared expression and activity of beta catenin and its regulators in normal lung cell WI38 and NSCLC cell A549 by western blot,qRT-PCR and luciferase assay.We observed that beta catenin positive regulators(Akt and Hsp90)and negative regulators(Gsk3 beta and microRNA-214)have differential expression and/or activity in NSCLC cell A549.However the differentially altered statuses of both the positive and negative regulators rendered cumulative positive effect on beta catenin expression and activity in A549.Our study thus suggests that chemotherapeutic modulations of regulating factors are crucial when abrogation and/or inhibition of key oncogenic proteins are necessary for cancer chemotherapy.展开更多
The role of nm23H1 genetic instability is not limited to gastrointestinal malignancies.A similar close relationship exists between nm23H1 genetic instability and other non gastrointestinal systemic malignancies.For in...The role of nm23H1 genetic instability is not limited to gastrointestinal malignancies.A similar close relationship exists between nm23H1 genetic instability and other non gastrointestinal systemic malignancies.For instance,in oral malignant melanomas with lymphoid metastasis,the nm23H1 expression is significantly lower in contrast to tumors with no lymphoid metastasis.Similarly,increased metastasis is seen in non small cell lung cancers following down regulation of nm23H1 in conjunction with KAI-1 down regulation. There is an inverse relationship between tumor stage and metastasis and nm23H1 expression in individuals with prostate carcinomas and a similar relationship exists between microsatellite instability of the nm23H1 gene and ovarian carcinogenesis.For instance,nearly 70.5%of stageⅠ-Ⅱovarian tumors express nm23H1 in sharp contrast to only 25%of stageⅢ-Ⅳovarian tumors.As is clearly evident,nm23H1 has a major role in gastrointestinal and non-gastrointestinal carcinogenesis.The coming few years will hopefully see the development of new strategies by virtue of which we can alter nm23H1 expression and thus decrease the risk of metastasis in malignant tumors.展开更多
According to WHO, cancer is a leading cause of death worldwide, accounting for 8.2 million deaths in 2012. Among several factors involved in the pathogenesis of cancer, free radical formation followed by damage to DNA...According to WHO, cancer is a leading cause of death worldwide, accounting for 8.2 million deaths in 2012. Among several factors involved in the pathogenesis of cancer, free radical formation followed by damage to DNA and cell protein is one of the causes. Natural plant products have gained enormous interest in the prevention or treatment of chronic diseases. Ferulic acid, like other phenolic acids (caffeic acid, sinapic acid) possess anti cancer activity. A series of ferulic esters (FE1 - FE11) and ferulic amides (FA1 - FA10) were synthesized and evaluated for their cytotoxic activity.展开更多
Arisaema heterophyllum Blume is one of the three medicinal plants known as traditional Chinese medicine Rhizoma Arisaematis(RA). RA has been popularly used to treat patients with convulsions, inflammation, and cancer ...Arisaema heterophyllum Blume is one of the three medicinal plants known as traditional Chinese medicine Rhizoma Arisaematis(RA). RA has been popularly used to treat patients with convulsions, inflammation, and cancer for a long time. However, the underlying mechanisms for RA effects are still unclear. The present study was designed to determine the cytotoxicity of agglutinin isolated from Arisema heterophyllum Blume(AHA) and explore the possible mechanisms in human non-small-cell lung cancer A549 cells. AHA with purity up to 95% was isolated and purified from Arisaema heterophyllum Blume using hydrophobic interaction chromatography. AHA dose-dependently inhibited the proliferation of A549 cells and induced G_1 phase cell cycle arrest. AHA induced apoptosis by up-regulating pro-apoptotic Bax, decreasing anti-apoptotic Bcl-2, and activating caspase-9 and caspase-3. In A549 cells treated with AHA, the PI3K/Akt pathway was inhibited. Furthermore, AHA induced increase in the levels of ER stress markers such as phosphorylated eukaryotic initiation factor 2α(p-eIF2α), C/EBP-homologous protein(CHOP), inositol-requiring enzyme 1α(IRE1α), and phosphorylated c-Jun NH_2-terminal kinase(p-JNK). AHA also induced autophagy in A549 cells. Staining of acidic vesicular organelles(AVOs) and increase in the levels of LC3II and ATG7 were observed in AHA-treated cells. These findings suggested that AHA might be one of the active components with anti-cancer effects in Arisaema heterophyllum Blume. In conclusion, cytotoxicity of AHA on cancer cells might be related to its effects on apoptosis and autophagy through inhibition of PI3K/Akt pathway and induction of ER stress.展开更多
Objective:To define the properties of lung cancer cells that resisted conventionally fractionated radiation exposure.Methods:Acquired radioresistant lung cancer cell line A549 was constructed by X-ray irradiation with...Objective:To define the properties of lung cancer cells that resisted conventionally fractionated radiation exposure.Methods:Acquired radioresistant lung cancer cell line A549 was constructed by X-ray irradiation with a clinical conventional fraction dose of 2 Gy daily during 30 fractions.Cell morphology,molecular markers,migration capacity and invasion potential were evaluated by the microscope,Western blot,immunofluorescence,wound healing test and transwell chamber assay,respectively.Results:Radioresistant A549 cells shifted from an epithelial to a mesenchymal morphology,termed as epithelial-mesenchymal transition(EMT),and was accompanied by decreased expressions of epithelial markers(F=4.568,P<0.05)and increased expression of mesenchymal markers(F=4.270,P<0.05),greater migratory and invasive capabilities(t=6.386,5.644,P<0.05).The expression of TGF-β,and phosphorylated levels of Akt and Smad3 were also enhanced(F=6.496,4.685,3.370,P<0.05).Furthermore,the EMT phenotype induced by radiation could be reversed through inhibition of TGF-β,Akt or Smad3,indicating a functional relationship be-tween them.Conclusions:EMT mediates acquired radioresistance of lung cancer cells induced by IR with clinical parameters,and the crosstalk mode of TGF-β/Akt/Smad signaling plays a critical regulatory role in this process.展开更多
Coriolus versicolor has demonstrated anti-cancer effects via polysaccharide-peptides(PSP)and polysaccharide Krestin(PSK).However,many other bioactive compounds within Coriolus versicolor(CV)may not have been identifie...Coriolus versicolor has demonstrated anti-cancer effects via polysaccharide-peptides(PSP)and polysaccharide Krestin(PSK).However,many other bioactive compounds within Coriolus versicolor(CV)may not have been identified.Our primary focus was to determine whether the ethanolic extract of Coriolus versicolor demonstrated any anti-cancer effects.The crude ethanolic extract was utilized,as was展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81972763 and 81473241).
文摘In the present study,we introduced the H2O2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine(GEM)to synthesize a new target compound named GEM-ZZQ,and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy.We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could be activated by H2O2 to release GEM.Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM.For the lung cancer cell lines that are resistant to the epidermal growth factor receptor(EGFR)-targeting inhibitor osimertinib,GEM-ZZQ showed less growth inhibition than GEM;however,GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups.In summary,we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying the GEM structure.
基金supported by Lebanese University for the financial support of this work(Project M.Nasser UL2017)
文摘Objective: To test the coalescence effect of two chemotherapy drugs at low effective dose(cisplatin and taxotere) combined with pomegranate juice on A549 cancer cells. Methods: Infrared spectroscopy method is a qualitative test that was performed to ensure the existence of the phytochemicals providing the antioxidant activity through the presence of the hydroxyl group(-OH). The viability of A549 cell line and normal MCs was tested using the neutral red uptake, Clonogenic survival, XTT and Cell migration assays. Results: Our results showed that this combination firstly led to a greater decrease in the viability of cells comparing to those treated with chemotherapy drugs alone, and secondly led to a significant reduction in cell migration. Conclusions: These data suggest a synergistic effect between the pomegranate and cisplatin which makes probably this combination a powerful option for treating lung adenocarcinoma and in parallel minimizing the systemic side effects.
基金Supported by the Natural Science Foundation of Jilin Province China(No.20090461)
文摘Alantolactone is a natural compound identified from the roots of Inula helenium L. that has multiple bio-activities. We examined its inhibitory effects on human non-small cell lung cancer（NSCLC） A549 cells. The an-tiproliferative effect of alantolactone on A549 cells was investigated via MTT[3′-（4,5dimethylthiazol-2-yl）-2,5- diphenyl tetrazolium bromide] assay and its apoptosis-inducing effect was determined by Hoechst staining and flow cytometry. We found that alantolactone significantly inhibited the proliferation of A549 cells and induced morphological changes typical for apoptosis. Flow cytometry analysis indicates dose-dependent cell cycle retardation at G0/G1 and S stages. The results indicate that alantolactone could be an attractive small-molecular natural compound for further development as a therapeutic drug against NSCLC.
基金supported by the National Natural Science Foundation of China(No.314 008 55)the Technological Innovation Incubator Program from Henan University of Technology(No.201 518)the Introduced Postdoctoral Talents of Henan University of Technology(No.150 199)
文摘Cell labeling with magnetic iron oxide nanoparticles(IONPs)is increasingly a routine approach in the cellbased cancer treatment.However,cell labeling with magnetic IONPs and their leading effects on the biological properties of human lung carcinoma cells remain scarcely reported.Therefore,in the present study the magnetic c-Fe2O3nanoparticles(MNPs)were firstly synthesized and surface-modified with cationic poly-L-lysine(PLL)to construct the PLL-MNPs,which were then used to magnetically label human A549 lung cancer cells.Cell viability and proliferation were evaluated with propidium iodide/fluorescein diacetate double staining and standard 3-(4,5-dimethylthiazol-2-diphenyl-tetrazolium)bromide assay,and the cytoskeleton was immunocytochemically stained.The cell cycle of the PLL-MNPlabeled A549 lung cancer cells was analyzed using flow cytometry.Apoptotic cells were fluorescently analyzed with nuclear-specific staining after the PLL-MNP labeling.The results showed that the constructed PLL-MNPs efficiently magnetically labeled A549 lung cancer cells and that,at low concentrations,labeling did not affect cellular viability,proliferation capability,cell cycle,and apoptosis.Furthermore,the cytoskeleton in the treated cells was detected intact in comparison with the untreated counterparts.However,the results also showed that at high concentration(400 lg m L-1),the PLL-MNPs would slightly impair cell viability,proliferation,cell cycle,and apoptosis and disrupt the cytoskeleton in the treated A549 lung cancer cells.Therefore,the present results indicated that the PLL-MNPs at adequate concentrations can be efficiently used for labeling A549 lung cancer cells and could be considered as a feasible approach for magnetic targeted anti-cancer drug/gene delivery,targeted diagnosis,and therapy in lung cancer treatment.
文摘Objective Loss-of-function mutation of p53,a tumor suppressor gene,is an important mechanism for the development of human cancers. In this study we tried to transfect p53N15-based fusion peptide into H1299,a lung cancer cell line,and evaluate the anti-tumor effects of the fusion peptide. Methods Adeno-associated virus (AAV) vectors were used for transfecting p53N15 fusion peptide into p53-null lung adenocarcinoma H1299 cells.
文摘Objective： To study the inhibition of Cantharidin against the proliferation of human lung cancer A549 cells and its mechanism. Methods： MTT assay was employed to determine the inhibition of Cantharidin against proliferation of A549 cells and flow Cytometry was applied to analyze A549 cell cycle and the effect of Cantharidin on cell cycle. Results： Cantharidin showed inhibition against the proliferation of A549 cells, and the inhibition was mediated by blocking A549 cell cycle at G2/M phase significantly. Conclusion： Cantharidin exhibits inhibition against the proliferation of human lung cancer A549 cells.
文摘BACKGROUND The most common EGFR mutations are in-frame deletions in exon 19 and point mutations in exon 21.Cases with classical EGFR mutations show a good response to EGFR tyrosine kinase inhibitors(TKIs),the standard first-line treatment.With the development of next generation sequencing,some uncommon genomic mutations have been detected.However,the effect of TKIs on such uncommon EGFR mutations remains unclear.CASE SUMMARY Here,we report a case of rare EGFR co-mutation in non-small cell lung cancer and the efficacy of afatinib on this EGFR co-mutation.A 64-year-old woman was diagnosed with thoracolumbar and bilateral local rib bone metastases,bilateral pulmonary nodules,and pericardial and left pleural effusion.The pathological diagnosis was lung adenocarcinoma.To seek potential therapeutic regimens,rare co-mutation comprising rare EGFR G724S/R776H mutations and amplification were identified.The patient experienced a significant clinical response with a progression-free survival of 17 mo.CONCLUSION A case of non-small cell lung cancer with rare EGFR G724S/R776H mutations and EGFR amplification responds well to TKI treatment.
文摘Objective To observe the effect of Fuzheng Kang’ai Recipe(FKR)combined with gefitinib on the proliferation and apoptosis of lung cancer A549 cells,and to study its potential synergistic mechanish with gefitinib.Methods The effects of FKR(0.211,0.316,0.474,0.711,1.067,1.600,2.400,3.600 mg/mL)combined with
基金This work was supported by DAE,Government of India.We thank Prof.Nitai Pada Bhattacharyya,Former Professor,Saha Institute of Nuclear Physics,Kolkata-700064 for providing the empty U61 and miR-214-U61 plasmids and primers of U6 snRNA and miR-214.
文摘Beta catenin has been well documented in previous studies to be involved in non small cell lung cancer(NSCLC).Beta catenin abundance and transcriptional activity are significantly regulated by several factors.Though it is well known that Akt and Gsk3 beta are respective positive and negative regulators of beta catenin,however,no single study has so far documented how the expression and activity of both positive as well as negative regulators play favorable role on beta catenin expression and activity in NSCLC.In this study,we compared expression and activity of beta catenin and its regulators in normal lung cell WI38 and NSCLC cell A549 by western blot,qRT-PCR and luciferase assay.We observed that beta catenin positive regulators(Akt and Hsp90)and negative regulators(Gsk3 beta and microRNA-214)have differential expression and/or activity in NSCLC cell A549.However the differentially altered statuses of both the positive and negative regulators rendered cumulative positive effect on beta catenin expression and activity in A549.Our study thus suggests that chemotherapeutic modulations of regulating factors are crucial when abrogation and/or inhibition of key oncogenic proteins are necessary for cancer chemotherapy.
文摘The role of nm23H1 genetic instability is not limited to gastrointestinal malignancies.A similar close relationship exists between nm23H1 genetic instability and other non gastrointestinal systemic malignancies.For instance,in oral malignant melanomas with lymphoid metastasis,the nm23H1 expression is significantly lower in contrast to tumors with no lymphoid metastasis.Similarly,increased metastasis is seen in non small cell lung cancers following down regulation of nm23H1 in conjunction with KAI-1 down regulation. There is an inverse relationship between tumor stage and metastasis and nm23H1 expression in individuals with prostate carcinomas and a similar relationship exists between microsatellite instability of the nm23H1 gene and ovarian carcinogenesis.For instance,nearly 70.5%of stageⅠ-Ⅱovarian tumors express nm23H1 in sharp contrast to only 25%of stageⅢ-Ⅳovarian tumors.As is clearly evident,nm23H1 has a major role in gastrointestinal and non-gastrointestinal carcinogenesis.The coming few years will hopefully see the development of new strategies by virtue of which we can alter nm23H1 expression and thus decrease the risk of metastasis in malignant tumors.
文摘According to WHO, cancer is a leading cause of death worldwide, accounting for 8.2 million deaths in 2012. Among several factors involved in the pathogenesis of cancer, free radical formation followed by damage to DNA and cell protein is one of the causes. Natural plant products have gained enormous interest in the prevention or treatment of chronic diseases. Ferulic acid, like other phenolic acids (caffeic acid, sinapic acid) possess anti cancer activity. A series of ferulic esters (FE1 - FE11) and ferulic amides (FA1 - FA10) were synthesized and evaluated for their cytotoxic activity.
基金supported by the National Nature Science Foundation of China(No.81373964)Shanghai Science&Technology Support Program(No.13431900401)+1 种基金Shanghai Science&Technology Innovation Action Program(No.15140904800)the National Science&Technology Major Project of China(No.2014 ZX09301-306-03)
文摘Arisaema heterophyllum Blume is one of the three medicinal plants known as traditional Chinese medicine Rhizoma Arisaematis(RA). RA has been popularly used to treat patients with convulsions, inflammation, and cancer for a long time. However, the underlying mechanisms for RA effects are still unclear. The present study was designed to determine the cytotoxicity of agglutinin isolated from Arisema heterophyllum Blume(AHA) and explore the possible mechanisms in human non-small-cell lung cancer A549 cells. AHA with purity up to 95% was isolated and purified from Arisaema heterophyllum Blume using hydrophobic interaction chromatography. AHA dose-dependently inhibited the proliferation of A549 cells and induced G_1 phase cell cycle arrest. AHA induced apoptosis by up-regulating pro-apoptotic Bax, decreasing anti-apoptotic Bcl-2, and activating caspase-9 and caspase-3. In A549 cells treated with AHA, the PI3K/Akt pathway was inhibited. Furthermore, AHA induced increase in the levels of ER stress markers such as phosphorylated eukaryotic initiation factor 2α(p-eIF2α), C/EBP-homologous protein(CHOP), inositol-requiring enzyme 1α(IRE1α), and phosphorylated c-Jun NH_2-terminal kinase(p-JNK). AHA also induced autophagy in A549 cells. Staining of acidic vesicular organelles(AVOs) and increase in the levels of LC3II and ATG7 were observed in AHA-treated cells. These findings suggested that AHA might be one of the active components with anti-cancer effects in Arisaema heterophyllum Blume. In conclusion, cytotoxicity of AHA on cancer cells might be related to its effects on apoptosis and autophagy through inhibition of PI3K/Akt pathway and induction of ER stress.
基金supported by grants from the National Natural Science Foundation of China(No.31200633)Anhui Provincial Natural Science Foundation(No.2008085MH245)+2 种基金Excellent Young Talent Support Project of Anhui Educational Committee(No.GXYQ2019036)Natural Science Research Project of Anhui Educational Committee(No.KJ2018A0241)512 Talent Project and Natural Science Foundation of Bengbu Medical College(No.BY51201211,BYKY1725ZD).
文摘Objective:To define the properties of lung cancer cells that resisted conventionally fractionated radiation exposure.Methods:Acquired radioresistant lung cancer cell line A549 was constructed by X-ray irradiation with a clinical conventional fraction dose of 2 Gy daily during 30 fractions.Cell morphology,molecular markers,migration capacity and invasion potential were evaluated by the microscope,Western blot,immunofluorescence,wound healing test and transwell chamber assay,respectively.Results:Radioresistant A549 cells shifted from an epithelial to a mesenchymal morphology,termed as epithelial-mesenchymal transition(EMT),and was accompanied by decreased expressions of epithelial markers(F=4.568,P<0.05)and increased expression of mesenchymal markers(F=4.270,P<0.05),greater migratory and invasive capabilities(t=6.386,5.644,P<0.05).The expression of TGF-β,and phosphorylated levels of Akt and Smad3 were also enhanced(F=6.496,4.685,3.370,P<0.05).Furthermore,the EMT phenotype induced by radiation could be reversed through inhibition of TGF-β,Akt or Smad3,indicating a functional relationship be-tween them.Conclusions:EMT mediates acquired radioresistance of lung cancer cells induced by IR with clinical parameters,and the crosstalk mode of TGF-β/Akt/Smad signaling plays a critical regulatory role in this process.
文摘Coriolus versicolor has demonstrated anti-cancer effects via polysaccharide-peptides(PSP)and polysaccharide Krestin(PSK).However,many other bioactive compounds within Coriolus versicolor(CV)may not have been identified.Our primary focus was to determine whether the ethanolic extract of Coriolus versicolor demonstrated any anti-cancer effects.The crude ethanolic extract was utilized,as was
