Silibinin-induced mitochondria fission leads to mitophagy, which attenuates silibinin-induced apoptosis in MCF-7 and MDA-MB-231 cells

摘要: Abstract We reported previously that higher doses (150–250 μM) of silibinin enhanced fission and inhibited fusion mitochondria, accompanying apoptosis double-positive breast cancer cell line MCF-7 cells triple-negative MDA-MB-231 cells. report here three important questions yet unclarified in the previous study; 1) Whether mitochondria by treatment leads to mitophagy, 2) mitophagy positively contributes 3) estrogen receptor-positive (ER+) receptor-negative (ER−) MDA-MB-231 cells are affected a different way treatment, since often works through ERs signaling pathway. Mitophagy driven Pink1/Parkin signaling, plays an role eliminating damaged mitochondria. Indeed, increased expression Pink1 recruitment Parkin LC3-II with account for induction mitophagy. In this study, effects mitochondrial division inhibitor 1 (mdivi-1) small interfering RNA targeting dynamin-related protein (DRP1) were examined reveal effect on As expected, mdivi-1 or siRNA DRP1 reversed silibinin-induced due down-regulation DRP1. Inhibition prevented as well autophagy both MCF-7 MDA-MB-231 cells, indicating efficiently our work, second point present inhibition knockdown these cells, respectively, suggesting induced serves cytoprotective effect, resulting reduction cells cells. third point, we studied whether receptors (ERs) played ERα ERβ not involved mitophagic process These findings demonstrated which attenuates ERs-Pink1 -Parkin pathway MDA-MB-231.