Objective:To explore the therapeutic effects of the novel wild edible mushroom Astraeus hygrometricus(Pers.)Morgan(A.hygrometricus)on human acute lymphoblastic leukemia cells.Methods:Extensive screening of the antipro...Objective:To explore the therapeutic effects of the novel wild edible mushroom Astraeus hygrometricus(Pers.)Morgan(A.hygrometricus)on human acute lymphoblastic leukemia cells.Methods:Extensive screening of the antiproliferative and chemopreventive potential of different extracts from 5 wild mushrooms,A.hygrometricus,Phallus sp.,Lentinus sp.,Tricholoma sp.,and Serpula sp.was performed against a panel of 6 cancer cell lines and normal cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Apoptosis determination,cell cycle profiling,intracellular reactive oxygen species(ROS)and reactive nitrogen species(RNS),and mitochondrial membrane potential were analyzed by flow cytometry.The activity of caspases was measured colorimetrically,and the expression pattern of mitochondrial proteins was analyzed.Results:The methanol extract of A.hygrometricus and MOLT-4 cells were identified as the most potent extract exhibiting antiproliferative activity and most sensitive cell line,respectively.The mushroom extract induced robust selective apoptosis in MOLT-4 cells and arrested cell cycle progression at the G0/G1 stage.The extract disrupted the mitochondrial membrane potential and enhanced ROS production in MOLT-4 cells.The methanol extract induced apoptosis by downregulating the expression of Bcl-2,increasing the expression of Bax,and activating the caspase cascade.Conclusion:The novel wild edible mushroom is a potential repository of biomolecules for the development of antileukemic drugs.展开更多
Background:Mushroom-derived components have immense potential to become a safe alternative in identifying lead anti-cancer molecules.Termitomyces heimii Natarajan(T.heimii)is a traditionally used edible mushroom with ...Background:Mushroom-derived components have immense potential to become a safe alternative in identifying lead anti-cancer molecules.Termitomyces heimii Natarajan(T.heimii)is a traditionally used edible mushroom with no previous record of anti-hepatocarcinoma activity.Methods:The anti-proliferative efficacy of the mushroom ethyl acetate extract was screened against a panel of seven cancer cell lines,namely Hep G2,MCF-7,MDA-MB-231,MAD-MB-436,MOLT-4,Reh,and K-562,and against peripheral blood mononuclear cells isolated from normal healthy donors by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay.The impact of the extract on nuclear morphology was examined by 40,6-diamidino-2-phenylindole staining and the apoptotic potential of the extract was evaluated through flow cytometry and Annexin V-PI dual staining,followed by an in vitro scratch assay to elucidate the anti-migratory potential of the extract.The apoptotic and antimigratory effects were further validated using in silico molecular docking with four compounds,ergosterol,ergosta-5,8-dien-3-ol,lanosterol,and eburicol,against two anti-apoptotic proteins,Bcl-2 and Bcl-XL,and two angiogenic receptors,VEGFR-1 and VEGFR-2.Results:The screening data revealed that ethyl acetate extract exhibited remarkable anti-proliferative efficacy against Hep G2 cells,with a half maximal inhibitory concentration(IC50)value of 263.53(8.09)mg/mL,followed by MCF-7 cell lines and showed a negligible effect on peripheral blood mononuclear cells.A clear alteration of the cellular and nuclear morphology was concentration-dependently observed in Hep G2 cells.The extract induced robust apoptosis and a significant concentrationdependent increase in the scratch area.The results of in silico docking revealed that compared to standard drug sunitinib,both ergosterol and ergosta-5,8-dien-3-ol displayed lower binding energy,and satisfactory drugability and absorption,distribution,metabolism,excretion,and toxicity properties.Conclusions:T.heimii is a potential source for isolating lead anticancer molecules in the future.Ergosterol and ergosta-5,8-dien-3-ol hold great promise as new drugs against hepatocarcinoma.展开更多
基金indebted toWest Bengal-Department of Science and Technology(1158[Sanc]/ST BT-13015/15/2021-ST SEC)for project funding,University Grants Commission for providing fellowship and contingency to Ribhu Ray,Indian Council of Medical Research for providing fellowship and contingency to Anirban Chouni and UGC-UPE and UGC-CAS program at the Department of Botany,University of Calcutta for financial support.
文摘Objective:To explore the therapeutic effects of the novel wild edible mushroom Astraeus hygrometricus(Pers.)Morgan(A.hygrometricus)on human acute lymphoblastic leukemia cells.Methods:Extensive screening of the antiproliferative and chemopreventive potential of different extracts from 5 wild mushrooms,A.hygrometricus,Phallus sp.,Lentinus sp.,Tricholoma sp.,and Serpula sp.was performed against a panel of 6 cancer cell lines and normal cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Apoptosis determination,cell cycle profiling,intracellular reactive oxygen species(ROS)and reactive nitrogen species(RNS),and mitochondrial membrane potential were analyzed by flow cytometry.The activity of caspases was measured colorimetrically,and the expression pattern of mitochondrial proteins was analyzed.Results:The methanol extract of A.hygrometricus and MOLT-4 cells were identified as the most potent extract exhibiting antiproliferative activity and most sensitive cell line,respectively.The mushroom extract induced robust selective apoptosis in MOLT-4 cells and arrested cell cycle progression at the G0/G1 stage.The extract disrupted the mitochondrial membrane potential and enhanced ROS production in MOLT-4 cells.The methanol extract induced apoptosis by downregulating the expression of Bcl-2,increasing the expression of Bax,and activating the caspase cascade.Conclusion:The novel wild edible mushroom is a potential repository of biomolecules for the development of antileukemic drugs.
基金WB-DSTBT (West Bengal Department of Science and Technology and Biotechnology,Sanction No.:1158(Sanc)/ST BT-13015/15/2021-ST SEC dated 15/02/2022) for funding the projectCSIR (Council of Scientific and Industrial Research)+1 种基金UGC (University Grants Commission) for providing fellowship and contingency to individual research scholarsthe UGC-UPE and UGC-CAS programs at the Department of Botany,University of Calcutta for providing financial support
文摘Background:Mushroom-derived components have immense potential to become a safe alternative in identifying lead anti-cancer molecules.Termitomyces heimii Natarajan(T.heimii)is a traditionally used edible mushroom with no previous record of anti-hepatocarcinoma activity.Methods:The anti-proliferative efficacy of the mushroom ethyl acetate extract was screened against a panel of seven cancer cell lines,namely Hep G2,MCF-7,MDA-MB-231,MAD-MB-436,MOLT-4,Reh,and K-562,and against peripheral blood mononuclear cells isolated from normal healthy donors by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay.The impact of the extract on nuclear morphology was examined by 40,6-diamidino-2-phenylindole staining and the apoptotic potential of the extract was evaluated through flow cytometry and Annexin V-PI dual staining,followed by an in vitro scratch assay to elucidate the anti-migratory potential of the extract.The apoptotic and antimigratory effects were further validated using in silico molecular docking with four compounds,ergosterol,ergosta-5,8-dien-3-ol,lanosterol,and eburicol,against two anti-apoptotic proteins,Bcl-2 and Bcl-XL,and two angiogenic receptors,VEGFR-1 and VEGFR-2.Results:The screening data revealed that ethyl acetate extract exhibited remarkable anti-proliferative efficacy against Hep G2 cells,with a half maximal inhibitory concentration(IC50)value of 263.53(8.09)mg/mL,followed by MCF-7 cell lines and showed a negligible effect on peripheral blood mononuclear cells.A clear alteration of the cellular and nuclear morphology was concentration-dependently observed in Hep G2 cells.The extract induced robust apoptosis and a significant concentrationdependent increase in the scratch area.The results of in silico docking revealed that compared to standard drug sunitinib,both ergosterol and ergosta-5,8-dien-3-ol displayed lower binding energy,and satisfactory drugability and absorption,distribution,metabolism,excretion,and toxicity properties.Conclusions:T.heimii is a potential source for isolating lead anticancer molecules in the future.Ergosterol and ergosta-5,8-dien-3-ol hold great promise as new drugs against hepatocarcinoma.
