Anticancer,Anti-inflammatory,Analgesic,and Anxiolytic Effects of Koumine and Their Molecular Mechanisms

Koumine is an indole alkaloid monomer extracted from the Chinese herb Gelsemium elegans,which has a variety of pharmacological effects.This paper provides a comprehensive summary of the pharmacological effects and molecular mechanisms of koumine,with a particular emphasis on its mechanisms of action in the context of anticancer,anti-inflammatory,analgesic,and anxiolytic properties.The aim is to provide a theoretical foundation for further research and the application of koumine in clinical practice.

The Anticancer Potential of Quassinoids-A Mini-Review

The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.

Cytotoxicity, Toxicity and Anticancer Activity of Manuka Honey, Saudi’s Honey and Peganum harmala Plant against Cancer Cells

Cancer occurs when the body’s cells grow beyond the usual control. Normal body cells multiply in a controlled manner and undergo apoptosis when the body no longer needs them. Different types of cancers exist, and the common ones include breast, cervical, prostate, lung, colon, and skin cancers. Several factors have been associated with cancers, and these factors include poor dieting, exposure to harmful chemicals and radiation, weak immune system, and genetics. Cancer presents an enormous health threat in the modern world and thus the need to identify an effective treatment. The conventional treatments used in the management of cancer include chemotherapy and physiotherapy. These forms of cancer treatments usually have enormous side effects on the subjects. In this respect, an alternative form of treatment would be effective in managing cancer patients. A substantial number of natural products have been observed to be effective in the management of cancer. These natural products include plants and other natural substances such as honey. This study focuses on the efficiency of natural products in the treatment of cancer. Also, the anticancer effects of Peganum harmala, Manuka honey, and Saudi honey will be analyzed. Bee honey and Peganum harmala have been traditionally used in the treatment of cancer. The extracts from Peganum harmala plant have also been shown to exhibit divers’ antitumor effects similar to the mode of action of a vast number of anticancer agents. These established hypotheses thus give the rationale for this study. In this experiment, extracts were obtained from Peganum harmala leaves and exposed to cervical, lung, and prostate cancer cells. Similarly, solutions of Manuka honey and Saudi honey were exposed to the cervical, lung, and prostate cancer cells. The experiment duration was 24 hours, which obtained results were recorded and analyzed. Peganum harmala extracts inhibit cancer cell growth at different and achievable concentrations. Manuka honey highly inhibits the growth of HeLa cancer cells while Saudi honey highly inhibits the growth of A549 cells. Peganum harmala can form an effective treatment for managing several types of cancers. Manuka Honey can be applied as an effective treatment for managing cervical cancer while Saudi honey can form an effective treatment for managing lung cancers.

Phytochemical profiling and anticancer potential of Cymbopogon citratus extract

Objective:To evaluate the anticancer potential of Cymbopogon citratus extract.Methods:GC-MS analysis was used to identify phytocomponents in the methanolic extract of Cymbopogon citratus.A fractionation method was employed to isolate and assess the bioactivity of different fractions and their cytotoxic activities against cancer cell lines HCT116,LoVo,Caco-2,and HT-29 were investigated.A dual staining method with acridine orange and ethidium bromide was used to assess the effect of the extract on cell apoptosis.Additionally,the expression levels of Bax and TP53 were quantified using real-time PCR in Caco-2 cells treated with the ethyl acetate fraction of Cymbopogon citratus extract.A protein array was employed to profile key pro-and anti-apoptotic proteins in Caco-2 cells.Moreover,molecular docking studies were conducted to investigate the interactions between key compounds of Cymbopogon citratus extract and specific apoptosis-related protein domains(PDB IDs:7wql and 4bkx).Results:A significant growth inhibition was observed in Caco-2 cells treated with Cymbopogon citratus extract.Among the seven fractions of the plant extract,the ethyl acetate fraction showed the highest cytotoxicity against Caco-2 cells with an IC50 value of(6.16±0.01)μg/mL.The immunofluorescence assay showed that the ethyl acetate fraction could induce apoptosis of Caco-2 cells.Moreover,the fraction upregulated the gene expressions of Bax and TP53 in a dose-dependent manner.The docking analysis demonstrated the interaction of five compounds isolated from the ethyl acetate fraction with key proteins in Caco-2 cells,indicating their anticancer properties.Conclusions:Cymbopogon citratus extract shows anticancer activity against Caco-2 cells by inducing apoptosis.It may be a promising candidate for the treatment of colon cancer,which needs further investigation.

Anticancer Activity of Rice Callus Suspension Cultures from Aromatic Varieties and Metabolites Regulated in Treated Cancer Cell Lines

Tissue culture techniques were used to produce large amounts of bioactive compounds with medicinal potential, overcoming space and time constraints for cancer prevention. Rice callus suspension cultures(RCSC) and seed extracts prepared from aromatic rice varieties were used to evaluate the cytotoxic impact on human colon and lung cancer cell lines, as well as a normal control cell line, using Taxol as a positive control. RCSC and seed extracts from two Indian aromatic rice varieties were applied at different concentrations to treat the cancer cell lines and normal lung fibroblasts over varying time intervals. Apoptosis was assessed in 1:5 dilutions of the A549 and HT-29 cell lines treated with RCSC for 72 h, using propidium iodide staining and flow cytometry. RCSC showed a more potent cytotoxic effect than seed extracts with minimal effect on the normal cell line, in contrast to Taxol. Confocal microscopy and flow cytometry further confirmed the apoptotic effect of RCSC. Gas chromatography-mass spectrometry-based metabolic profiling identified metabolites involved in cytotoxicity and highlighted altered pathways. RCSC is proposed as an alternative source for the development of novel anticancer drugs with reduced side effects.

Effects of invigorating-spleen and anticancer prescription on extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in colon cancer mice model

BACKGROUND Colon cancer(CC)is one of the most common malignant tumors in the gastrointestinal system.Overall,CC had the third highest incidence but the second highest mortality rate globally in 2020.Nowadays,CC is mainly treated with capecitabine chemotherapy regimen,supplemented by radiotherapy,immunotherapy and targeted therapy,but there are still limitations,so Chinese medicine plays an important role.AIM To investigate the effects of invigorating-spleen and anticancer prescription(ISAP)on body weight,tumor inhibition rate and expression levels of proteins in extracellular-signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)signaling pathway in CC mice model.METHODS The CC mice model were established and the mice were randomly divided into 5 groups,including the control group,capecitabine group,the low-dose,mediumdose and high-dose groups of ISAP,with 8 mice in each group,respectively.After 2 weeks of intervention,the body weight and tumor inhibition rate of mice were observed,and the expression of RAS,ERK,phosphorylated ERK(p-ERK),C-MYC and matrix metalloproteinase 2(MMP2)proteins in the tissues of tumors were detected.RESULTS Compared with the control group,the differences of body weight before and after treatment was much smaller in the groups of ISAP,with the smallest difference in the high-dose group of ISAP,while the capecitabine group had the greatest difference,indicating ISAP had a significant inhibiting effect on the growth of transplanted tumor in mice.The expression of RAS protein was decreased in the low-and medium-dose groups of ISAP,and the change of p-ERK was significant in the medium-and high-dose groups of ISAP.MMP2 protein expression was significantly decreased in both the low-dose and medium-dose groups of ISAP.There were no significant changes in ERK in the ISAP group compared to the capecitabine group,while RAS,MMP2,and C-MYC protein expression were reduced in the ISAP group.The expression level of C-MYC protein decreased after treated with ISAP,and the decrease was the most significant in the medium-dose group of ISAP.CONCLUSION ISAP has a potential inhibiting effect on transplanted tumor in mice,and could maintain the general conditions,physical strength and body weight of mice.The expression levels of RAS,p-ERK,MMP2 and c-myc were also decreased to a certain extent.By inhibiting the expression of upstream proteins,the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased.Therefore,it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins.

Factors Influencing Compliance with Safe Handling Requirements of Anticancer Agents by Nurses in a Tertiary Hospital-A Secondary Publication

Purpose:This research aimed to identify leading factors that affect nurses’compliance with the safe handling of anticancer agents.Methods:Data were collected from 114 nurses working in the university hospital and were analyzed through independent t-test,one-way ANOVA,Pearson’s correlation coefficient,and multiple regression analysis using SPSS25.0.Results:The average level of compliance with the safe handling of anticancer agents was 3.73±0.33 out of 5 points.Workplace safety culture(β=0.40,P<0.001)and knowledge of safe handling(β=0.18,P=0.030)had significant influences on nurses’compliance with the safe handling of anticancer agents.The explained variance for compliance was 28.3%.Conclusion:To enhance the implementation of safety management for anticancer agents,each institution should strive to support human and material resources and enhance specialization in the workplace safety culture through system improvement.Based on the results of this study,we suggest research for the development of a training program for anticancer agent safety management.

Calotropis procera:a review of molecular mechanisms,bioavailability,and potential anticancer property

Calotropisprocera(Cp)is a traditional medicinal plant that has attracted significant attention for its potential anticancer properties.This review consolidates current research on the Cp bioactive compounds found in Cp,including cardenolides,flavonoids,and terpenoids,which exhibit cytotoxic effects against various cancer cells.These compounds function through multiple mechanisms,such as inducing apoptosis,inhibiting cell proliferation,suppressing angiogenesis,and modulating oxidative stress.Preclinical studies demonstrate that Cp extracts effectively reduce tumor size and improve survival rates in animal models.Furthermore,Cp influences key signaling pathways like PI3K/Akt and NF-κB,which contribute to its anticancer potential.Its therapeutic effects extend beyond oncology,encompassing,antinociceptive,anticonvulsant,antimalarial,anthelmintic,antioxidant,antidiabetic,myocardial infarction prevention,schizontocidal,antimicrobial,anti-inflammatory,larvicidal,immunomodulatory,antiulcer,Antifertility,antidiarrheal,estrogenic,and Dermatophytic properties.Despite the promising preclinical data,further investigation is necessary to address challenges such as bioavailability,toxicity,and the standardization of Cp-based treatments.This review highlights the therapeutic promise of Cp as a complementary anticancer agent while emphasizing the need for rigorous clinical trials to confirm its safety and efficacy.

Anticancer,Anti-inflammatory and Antibacterial Effects of Aloin and Its Molecular Mechanism

Aloin is the main medicinal component extracted from Aloe vera.It is a natural anthraquinone compound,with anticancer,anti-inflammatory and antibacterial and other biological functions.This paper reviews the pharmacological action and related mechanisms of aloin,in order to provide a theoretical basis for the development and utilization of aloin.

Anti-inflammatory,Bacteriostatic and Anticancer Effects of Madecassoside

Madecassoside is a natural active component extracted from Centella asiatica.In recent years,a large number of studies have reported that madecassoside has a variety of biological activities,such as anticancer,anti-inflammatory and antibacterial effects,prevention and treatment of cardiovascular diseases,nerve damage,visceral damage and arthritis,and other pharmacological effects.In this paper,the pharmacological action and mechanism of madecassoside were reviewed to provide a theoretical basis for further research of madecassoside and drug development.

Anticancer Activities of Substituted Cinnamic Acid Phenethyl Esters on Human Cancer Cell Lines

Caffeic acid phenethyl ester (CAPE) and sixteen substituted cinnamic acid phenethyl esters were prepared via conventional procedures in order to test their in vitro anticancer activities by either MTT assay or SRB assay on six different human cancer cell lines. The results indicated that in the concentration of 10 μmol·L -1 the lead compound CAPE possessed anticancer activities against human HL 60, Bel 7402, and Hela cell lines, and two other compounds possessed potent anticancer activities against Bel 7402 and Hela cell lines.

Purification and Characterization of Cytotoxins from Agkistrodon acutus Venom and Their Anticancer Activity

Aim To investigate the anticancer activity of two new cytotoxins from thevenom of Agkistrodon acutus. Methods The venom was isolated by FPLC column chromatography consistingof DEAE Sepharose FF and Source 30S. The cytotoxic activity on tumor cells was detected by MITmethod. Purity and molecular weight were determined by SDS-PAGE (silver staining). Their stabilitiesto temperature and pH were also detected. Results Two pure cytotoxins named ACTX-6 and ACTX-8 wereobtained. Their molecular weights are 98 kDa and 27 kDa, respectively. ACTX-6 consists of twosubunits bonded together by disulfide bonds. Conclusion ACTX-6 and ATCX-8 have highest inhibitoryactivity on lung cancer cell A549. ACTX-6 is stable to heat while ACTX-8 not. ACTX-6 is stablebetween pH 7-9 and ACTX-8 between pH 6 - 9.

Cantharidin and Its Analogues:Anticancer and Ser/Thr Protein Phosphatase Inhibitory Activities

This paper mainly describes the anticancer activities and Ser/Thr protein phosphatase inhibitory activities of cantharidin and its analogues.

Synthesis and Anticancer Effect of gem-Difluoromethylenated Chrysin Derivatives

Ten gem-difluoromethylenated chrysin derivatives were prepared and their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of gem-difluoromethylenated chrysin derivatives had higher anticancer activity than chrysin.

Synthesis, characterization, and anticancer properties of rare earth complexes with Schiff base and o-phenanthroline

Five novel ternary complexes of the rare earth ions with o-phenanthroline（Phen） and Schiff base salicylaldehyde L-phenyla- lanine（KHL） were synthesized in ethanol. Their compositions were characterized by elemental analysis, molar conductance, ^1H NMR, FT-IR, and Raman spectra. The formulas of the complexes were verified to be RE（L）（Phen）Cl（H2O） （RE=La^3＋, Ce^3＋, Nd^3＋, Er^3＋, and Gd^3＋; L=Schiff base salicylaldehyde L-phenylalanine; phen=o-phenanthroline）. Methyl thiazolyl tetrazolium （MTT） colorimetry and flow cytometry were used to test the anticancer effect of the complexes with K562 tumor cell. The research showed that the complexes could inhibit K562 tumor cell＇s growth, generation, and induce apoptosis. The inhibition ratio was accelerated by increasing the dosage, and it had significant positive correlation with the medication dosage.

Plant-derived anticancer agents: A green anticancer approach

Cancer is a frightful disease and represents one of the biggest health-care issues for the human race and demands a proactive strategy for cure. Plants are reservoirs for novel chemical entities and provide a promising line for research on cancer. Hitherto, being effective, chemotherapy is accompanied by certain unbearable side effects. Nevertheless,plants and plant derived products is a revolutionizing field as these are Simple, safer, ecofriendly, low-cost, fast, and less toxic as compared with conventional treatment methods.Phytochemicals are selective in their functions and acts specifically on tumor cells without affecting normal cells. Carcinogenesis is complex phenomena that involves many signaling cascades. Phytochemicals are considered suitable candidates for anticancer drug development due to their pleiotropic actions on target events with multiple manners. The research is in progress for developing potential candidates(those can block or slow down the growth of cancer cells without any side effects) from these phytochemicals. Many phytochemicals and their derived analogs have been identified as potential candidates for anticancer therapy. Effort has been made through this comprehensive review to highlight the recent developments and milestones achieved in cancer therapies using phytomolecules with their mechanism of action on nuclear and cellular factors. Furthermore, drugs for cancer treatment and their limitations have also been discussed.

Aqueous extracts of microalgae exhibit antioxidant and anticancer activities

Objective:To investigate the antioxidant and anticancer activities of aqueous extracts of nine microalgal species.Methods:Variable percentages of major secondary metabolites(total phenolic content,terpenoids and alkaloids) as well as phycobiliprotein pigments(phycocyanin, allophycocyanin and phycoerythrin) in the aqueous algal extracts were recorded.Antioxidant activity of the algal extracts was performed using 2,2 diphenyl-1-picrylhydrazyl(DPPH) test and 2,2'azino-bis(ethylbenzthiazoline-6-sulfonic acid(ABTS.) radical cation assay.Anticancer efficiency of the algal water extracts was investigated against Ehrlich Ascites Carcinoma cell(EACC) and Human hepatocellular cancer cell line(HepG2).Results:Antioxidant activity of the algal extracts was performed using DPPH test and ABTS.^+ radical cation assays which revealed 30.1-72.4%and 32.0-75.9%respectively.Anticancer efficiency of the algal water extracts was investigated against Ehdich Ascites Carcinoma Cell(EACC) and Human Hepatocellular cancer cell line(HepG2) with an activity ranged 87.25%and 89.4%respectively.Culturing the promising cyanobacteria species;Nostoc muscorum and Oscillatoria sp.under nitrogen stress conditions(increasing and decreasing nitrate content of the normal BG11 medium,1.5 g/L),increased nitrate concentration(3,6 and 9 g/L) led to a remarkable increase in phycobilin pigments followed by an increase in both antioxidant and anticancer activities in both cyanobacterial species.While the decreased nitrate concentration(0.75,0.37 and 0.0 g/L) induced an obvious decrease in phycobilin pigments with complete absence of allophycocyanin in case of Oscillatoria sp.Conclusions:Nitrogen starvation(0.00 g/L nitrate) induced an increase and comparable antioxidant and anticancer activities to those cultured in the highest nitrate content.

Synthesis and anticancer activities of porphyrin induced anticancer drugs

In view of the property of porphyrin＇s accumulation selectively in tumor, the ftorafur was modified by binding a porphyrin block to improve its tumor targeting and reduce its side effects. These novel porphyrin derivatives and metal compounds were synthesized under mild conditions with satisfactory yield, and the constructions of all these new compounds were characterized by UV, IR, MS, ^1H NMR spectra and elementary analysis. Their anticancer activities were evaluated by MTT assay; the results indicated that the anticancer activities of compounds 4a-e were twice as high as that of ftorafur.

Molecular analysis and anticancer properties of two identified isolates,Fusarium solani and Emericella nidulans isolated from Wady El-Natron soil in Egypt against Caco-2(ATCC) cell line

Objective:To characterize,identify and investigate the anticancer properties of two new soil fungal isolates,Emericella nidulansand Fusarium solani isolated from Wady El-Natron in Egypt against colon cancer Caco-2(ATCCj cell line.Methods:Soil sample was cultured and two strains were chosen for morphological and phenotypical characterization.Partial sequences of the 18s rRNA gene and the internal transcribed spacer region ITS of the two isolates were amplified by PCR.Phylogenetic tree construction and analysis of the resulted multiple sequences from the two fugal isolates were also carried out.In vitro anticancer activity of the two strains was done against colon Caco-2 cancer cell line.Reverse transcription — PCR was carried out to detect level of expression of p53 in Caco-2 cell line.Results:HF.I displayed morphological and genotypic characteristics most similar to that of Fusarium solani while HF.2 was most similar to Emericella nidulans with high similarity of 99%and 97%respectively.The multiple sequence alignment of the two fungal isolates showed that,the maximum identical conserved domains in the 18s rRNA genes were identified with the nucleotide regions of Slst to 399th base pairs,88th to 525th base pairs respectively.While those in the ITS genes were identified with the nucleotide regions of 88th to 463rd and Slst to 274th.The two isolates showed IC<sub>50 value with（6.24±5.21） and（9.84±0.36） μ g/mL) concentrations respectively at 28h.Reverse transcription- PCR indicated that these cells showed high level of expression for p53 mRNA.Conclusions:The morphology and molecular analysis identified HF.1 and HF.2 to be Fusarium solani and Emericella nidulans;new isolates of anticancer producing fungi from Wady El-Natroon city in Egypt.Treatment with the two isolates caused P53 expression in Caco-2 cell line.These two isolates can be used as an anticancer agents.

Anticancer effect of the extracts from Polyalthia evecta against human hepatoma cell line(HepG2)

Objective:To investigate the anticancer activity of Polyalthia evecta(P.evecta)(Pierre) Finet & Gagnep against human hepatoma cell line(HepG2).Methods:The anticancer activity was based on(a) the cytotoxicity against human hepatoma cells(HepG2) assessed using a neutral red assay and(b) apoptosis induction determined by evaluation of nuclei morphological changes after DAP1 staining.Preliminary phytochemical analysis of the crude extract was assessed by HPLC analysis.Results:The 50% ethanol-water crude leaf extract of P.evecta(EW-L) showed greater potential anticancer activity with high cytotoxicity[IC_(50)=(62.8±7.3)μg/mL]and higher selectivity in HepG2 cells than normal Vero cells[selective index(SI)=7.9].The SI of EW-L was higher than the positive control,melphalan(SI=1.6) and the apoptotic cells(46.4±2.6)%induced by EW-L was higher than the melphalan(41.6±2.1)%(P<0.05).The HPLC chromatogram of the EW-L revealed the presence of various kinds of polyphenolics and flavonoids in it.Conclusions: P.evecta is a potential plant with anticancer activity.The isolation of pure compounds and determination of the bioactivity of individual compounds will be further performed.