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Induction of MicroRNA-9 Mediates Cytotoxicity of Curcumin Against SKOV3 Ovarian Cancer Cells

  • Zhao, Song-Feng (Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University) ;
  • Zhang, Xiao (Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University) ;
  • Zhang, Xiao-Jian (Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University) ;
  • Shi, Xiu-Qin (Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University) ;
  • Yu, Zu-Jiang (Provincial Key Laboratory of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University) ;
  • Kan, Quan-Cheng (Provincial Key Laboratory of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University)
  • Published : 2014.04.30

Abstract

Background: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells. Materials and Methods: SKOV3 ovarian cancer cells were treated with curcumin ($10-60{\mu}M$) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment. Results: Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells. Conclusions: The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.

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