Induction of autophagy by oleifolioside A in HCT-116 human colorectal cancer cells

Abstract

AbstractIn current study, we addressed the anti-cancer effect of oleifolioside A and its mechanism on the regulation of cell death in HCT-116 human colorectal cancer cells. Oleifolioside A inhibited HCT-116 cell proliferation and caused apoptosis associated with sequential activation of caspases 8 and 3, followed by PARP cleavage. Moreover, anti-LC3-positive granules and the increased LC3-II level were observed in HCT-116 cells treated with oleifolioside A, which is the specific characteristics of autophagy. Treatment of autophagy inhibiors, 3-MA and Wort, markedly accelerated the cell death by oleifolioside A and, furthermore, knockdown of Beclin-1 and Atg7 using shRNA increased oleifolioside A-induced apoptosis, suggesting a cytoprotective function of autophagy against oleifolioside A-triggered apoptosis. Treatment of HCT-116 cells with oleifolioside A time-dependently activated extracellular signal-regulated kinase (ERK). Oleifolioside A-induced autophagy was dramatically inhibited by pretreatment with an ERK inhibitor, U0126, which resulted in a marked reduction in cell viability. These findings indicate that oleifolioside A induce autophagy through ERK activation in HCT-116 cells and that autophagy suppression enhances apoptosis induced by oleifolioside A.