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Oleanolic acid induces mitophagy and chemosenzitises human colon carcinoma cells

Oleanolic acid (OA) has been shown to possess numerous beneficial health effects. However, the effect of OA on mitophagy in colon cancer cells is unknown. The current study aimed to investigate the mechanism of autophagy/mitophagy in the anticancer activity of OA in HCT116 human colon carcinoma cells. OA dose-dependently reduced viability of HCT116 cells, with IC50 29.8 μΜ. The expression of cleaved caspase-3 and PARP1 increased after OA treatment, suggesting that OA induces apoptosis in HCT116 cells. Concurrently, OA induced autophagy in cancer cells, evidenced by the increase in expression of Beclin-1, Atg5 and LC3B-II, which played a prosurvival role. The induction of mitophagy was suggested by increased expression of p62 and PINK1 and reduced expression of TOMM20, which colocalized with LC3B. OA also induced nuclear accumulation of FOXO3a and p- FOXO3a. The cytotoxic activity of OA coincided with downregulation of the PI3K/Akt and ERK1/2 pathways and activation of AMPK, JNK1 and p38. In addition, OA enhanced the cytotoxicity of 5-FU. Our results showed concomitant induction of apoptosis and survival autophagy/mitophagy in HCT116 cells by OA via modulation of key signaling pathways involved in tumorigenesis. Additionally, we showed chemosensitization of HCT116 cells to 5- FU by OA.

oleanolic acid ; colon cancer ; apoptosis ; autophagy ; mitophagy, 5-fluorouracil

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