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Coroglaucigenin induces senescence and autophagy in colorectal cancer cells

文献类型： 外文期刊

作者： Huang, Yong-Hao 1 ; Lei, Jing 1 ; Yi, Guo-Hui 1 ; Huang, Feng-Ying 1 ; Li, Yue-Nan 1 ; Wang, Cai-Chun 1 ; Sun, Yan 1 ; Da 1 ;

作者机构： 1.Hainan Med Coll, Key Lab Trop Dis & Translat Med, Minist Educ, Haikou, Hainan, Peoples R China

2.Hainan Med Coll, Hainan Prov Key Lab Trop Med, Haikou, Hainan, Peoples R China

3.Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Haikou, Hainan, Peoples R China

4.Hainan Med Coll, Publ Res Lab, Haikou, Hainan, Peoples R China

期刊名称：CELL PROLIFERATION （ 影响因子：6.831； 五年影响因子：6.154 ）

ISSN： 0960-7722

年卷期： 2018 年 51 卷 4 期

页码：

收录情况： SCI

摘要： Objectives: Coroglaucigenin (CGN), a natural product isolated from Calotropis gigantean by our research group, has been identified as a potential anti-cancer agent. However, the molecular mechanisms involved remain poorly understood. Materials and methods: Cell viability and cell proliferation were detected by MTT and BrdU assays. Flow cytometry, SA-beta-gal assay, western blotting and immunofluorescence were performed to determine CGN-induced apoptosis, senescence and autophagy. Western blotting, siRNA transfection and coimmunoprecipitation were carried out to investigate the mechanisms of CGN-induced senescence and autophagy. The anti-tumour activities of combination therapy with CGN and chloroquine were observed in mice tumour models. Results: We demonstrated that CGN inhibits the proliferation of colorectal cancer cells both in vitro and in vivo. We showed that the inhibition of cell proliferation by CGN is independent of apoptosis, but is associated with cell-cycle arrest and senescence in colorectal cancer cells. Notably, CGN induces protective autophagy that attenuates CGN-mediated cell proliferation. Functional studies revealed that CGN disrupts the association of Hsp90 with both CDK4 and Akt, leading to CDK4 degradation and Akt dephosphorylation, eventually resulting in senescence and autophagy, respectively. Combination therapy with CGN and chloroquine resulted in enhanced anti-tumour effects in vivo. Conclusions: Our results demonstrate that CGN induces senescence and autophagy in colorectal cancer cells and indicate that combining it with an autophagy inhibitor may be a novel strategy suitable for CGN-mediated anti-cancer therapy.

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