Barrientosiimonas humi ethyl acetate extract exerts cytotoxicity against MCF-7 and MDA-MB-231 cells via induction of apoptosis and cell cycle arrest

摘要

Objective:To elucidate the cytotoxic effect of the secondary metabolitesofBarrientosiimonas humi(B.humi)onMCF-7and MDA-MB-231humanbreastcancercellsanditsunderlying mechanisms of action.Methods:The extract was obtained from the fermentation of B.humi and fractionation of the crude extract was conducted via column chromatography.Cytotoxicity of theB.humi extract was determinedbyusingMTTassayandreal-timecellularanalysis.Morphological changes,cell cycle profiles,mode of cell death,and caspase expressions of control and treated breast cancer cells were determined.Results:The ethyl acetate extract isolated from B.humi was cytotoxicagainst MCF-7 and MDA-MB-231celllines.Oneof thedichloromethane(DCM)fractions,designatedasDCM-F2,exhibited the strongest activity among all the fractions and thereby was selected for further studies.DCM-F2 had selective cytotoxicity on target cells by inducing apoptosis,particularly in the early stage,and cell cycle arrest.Treated cells caused inhibition of cell cycle progression at 72 h leading to a significant increase(P<0.05)in the G0/G1 population.DCM-F2 treated MDA-MB-231 cells showed caspase-dependent apoptosis,whereas DCM-F2 treated MCF-7 cells showed a caspase-independent apoptosis pathway.Five compounds were successfully isolated from B.humi.Cyclo(Pro-Tyr)was the most cytotoxic and selective compound against MCF-7 cells.Conclusions:B.humi ethyl acetate extract exhibits significant cytotoxicity against MCF-7 and MDA-MB-231 cells via induction of apoptosis and cell cycle arrest.