Cucurbitacin I induces pro-death autophagy in A549 cells via the ERK-mTOR-STAT3 signaling pathway

Natural Products are a great source of Cancer chemotherapeutic agents. In the present study, the Anticancer effects of cucurbitacin I on A549 cells were investigated. Cucurbitacin I decreased cell viability, inhibited colony formation, and induced Apoptosis in A549 cells. Cucurbitacin I caused accumulation of autophagosome and dose-dependent expression of LC3II protein. Autophagy inhibitors 3-methyladenine (3-MA) inhibited Autophagy induced by cucurbitacin I and relieved cucurbitacin I-triggered cell death and Apoptosis in A549 Cells. Cucurbitacin I treatment inhibits the ERK activation and the downstream phosphorylation level of mTOR and STAT3, but not the PI3K/Akt pathway. Furthermore, treatment with the mTOR Activator MHY-1485, which also suppressed cucurbitacin I-induced LC3II expression, and also reversed cucurbitacin I-induced cell death and Apoptosis. Taken together, these results suggest that cucurbitacin I induced pro-death Autophagy through ERK/mTOR/STAT3 signaling cascade in A549 cells.