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Curcumin induces apoptotic cell death and protective autophagy by inhibiting AKT/mTOR/p70S6K pathway in human ovarian cancer cells

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Curcumin (Cur), a yellow-colored dietary flavor from the plant (Curcuma longa), has been demonstrated to potentially resist diverse diseases, including ovarian cancer, but drug resistance becomes a major limitation of its success clinically. The key molecule or mechanism associated with curcumin resistance in ovarian cancer still remains unclear. The aim of our study was to investigate the effects of curcumin on autophagy in ovarian cancer cells and elucidate the underlying mechanism.

Methods

In our study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), EdU proliferation assay and colony-forming assay were used to assess cell viability. Apoptosis was detected by western blot and flow cytometric analysis of apoptosis. Autophagy was defined by both electron microscopy and immunofluorescence staining markers such as microtubule-associated protein 1 light chain 3 (LC3). Plasmid construction and shRNA transfection helped us to confirm the function of curcumin.

Results

Curcumin reduced cell viability and induced apoptotic cell death by MTT assay in human ovarian cancer cell lines SK-OV-3 and A2780 significantly. Electron microscopy, western blot and immunofluorescence staining proved that curcumin could induce protective autophagy. Moreover, treatment with autophagy-specific inhibitors or stable knockdown of LC3B by shRNA could markedly enhance curcumin-induced apoptosis. Finally, the cells transiently transfected with AKT1 overexpression plasmid demonstrated that autophagy had a direct relationship with the AKT/mTOR/p70S6K pathway.

Conclusions

Curcumin can induce protective autophagy of human ovarian cancer cells by inhibiting the AKT/mTOR/p70S6K pathway, indicating the synergistic effects of curcumin and autophagy inhibition as a possible strategy to overcome the limits of current therapies in the eradication of epithelial ovarian cancer.

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Funding

This study was supported by Grants from Natural Science Foundation of Shandong Province (ZR2016HM27) and Science Foundation of Qilu Hospital of Shandong University (no. 2016QLQN27).

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Author notes

  1. Rui-ying Dong and Pei-shu Liu contributed equally.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, Shandong, People’s Republic of China

    Li-dong Liu, Ying-xin Pang, Xin-rui Zhao, Rui Li, Cheng-juan Jin, Jing Xue, Rui-ying Dong & Pei-shu Liu

  2. Gynecology Oncology Key Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China

    Li-dong Liu, Ying-xin Pang, Xin-rui Zhao, Rui Li, Cheng-juan Jin, Jing Xue, Rui-ying Dong & Pei-shu Liu

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  1. Li-dong Liu
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Contributions

LL: protocol and project development, data management, data analysis, manuscript writing and manuscript editing. YP: protocol and project development, manuscript editing. XZ: data curation, formal analysis. RL: manuscript editing. CJ: manuscript editing. JX: manuscript editing. RD: resources, supervision. PL: protocol and project development, funding acquisition, supervision.

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Correspondence to Rui-ying Dong or Pei-shu Liu.

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Liu, Ld., Pang, Yx., Zhao, Xr. et al. Curcumin induces apoptotic cell death and protective autophagy by inhibiting AKT/mTOR/p70S6K pathway in human ovarian cancer cells. Arch Gynecol Obstet 299, 1627–1639 (2019). https://doi.org/10.1007/s00404-019-05058-3

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