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 4',6-diamidino-2-phenylindole staining and the apoptotic po-tential 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 anti-migratory 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(ICso)value of 263.53(8.09)ug/mL,followed by MCF-7 cell lines and showed a negligible effect on peripheral blood mono-nuclear 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 concentration-dependent 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.

Laboratory of Cell and Molecular Biology,Department of Botany,University of Calcutta,Kolkata,700019,West Bengal,India

[1]Ribhu Ray;Saparja Saha;Santanu Paul-.Two novel compounds,ergosterol and ergosta-5,8-dien-3-ol,from Termitomyces heimii Natarajan demonstrate promising anti-hepatocarcinoma activity)[J].中医科学杂志（英文）,2022(04):443-453

heimii,Natarajan,Reh,lanosterol,eburicol,drugability,Ergosterol

Two,novel,compounds,ergosterol,ergosta,dien,from,Termitomyces,demonstrate,promising,hepatocarcinoma,activity,Background,Mushroom,derived,components,have,immense,potential,become,safe,alternative,identifying,lead,molecules,traditionally,used,edible,mushroom,previous,record,Methods,proliferative,efficacy,acetate,extract,was,screened,against,panel,seven,lines,namely,Hep,G2,MCF,MB,MAD,MOLT,peripheral,blood,mononuclear,cells,isolated,normal,healthy,donors,by,dimethylthiazol,diphenyltetrazolium,bromide,reduction,assay,impact,morphology,examined,diamidino,phenylindole,staining,apoptotic,evaluated,through,flow,cytometry,Annexin,dual,followed,vitro,scratch,elucidate,migratory,effects,were,further,validated,using,silico,molecular,docking,four,two,proteins,Bcl,XL,angiogenic,receptors,VEGFR,Results,screening,data,revealed,that,exhibited,remarkable,half,maximal,inhibitory,concentration,ICso,value,showed,negligible,alteration,cellular,dependently,observed,induced,robust,apoptosis,significant,increase,area,results,compared,standard,sunitinib,both,displayed,lower,binding,energy,satisfactory,absorption,distribution,metabolism,excretion,toxicity,properties,Conclusions,source,isolating,anticancer,future,hold,great,promise,new,drugs

0.506559