Cucurbitacin E induces autophagy in HeLa cells by inhibiting mTORC1 activity

VernacularTitle:葫芦素E抑制HeLa细胞mTORC1的活性并诱导细胞自噬
Author: Xiaoyu ZHANG ; Lihui XU ; Gaoxiang ZHAO ; Hao PAN ; Dan ZHOU ; Dongyun OUYANG ; Xianhui HE
Publication Type:Journal Article
Keywords: cucurbitacin E; mTORC1; LC3-II; p70 S6 K; HeLa cells; autophagy
From: Chinese Pharmacological Bulletin 2014;(6):807-811
CountryChina
Language:Chinese
Abstract: Aim To study the mechanism of cucurb-itacin E ( CuE )-induced autophagy in HeLa cells. Methods Improved MTT assay was adopted to meas-ure the effect of CuE on cell proliferation. Western blot was used to determine the phosphorylation levels of downstream signaling proteins of mTORC1 and the ex-pression of autophagy associated proteins. ResultsCuE inhibited the proliferation of HeLa cells in a dose-dependent manner, and the 24-h IC50 of CuE was 4. 01μmol· L-1 . CuE significantly inhibited the phospho-rylation of p70 S6 K in a time-and dose-dependent man-ner as evidenced by decreased phosphorylation levels of
the mTORC1 substrate. Meanwhile, the expression of LC3-II, a marker for autophagosome formation, was elevated by CuE treatment, and was further increased in the presence of chloroquine. Furthermore, CuE re-duced the levels of p62/SQSTM1 . These results indi-cated that CuE induced autophagy in HeLa cells. The decreased levels of phosphorylated ULK1 S757 were posi-tively correlated with autophagy induction in HeLa cells. Conclusion CuE is likely to induce autophagy through inhibiting mTORC1 activity.