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

Background: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has showncytotoxic 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 ovariancancer cells were treated with curcumin (10-60 μM) and miR-9 expression, cell proliferation, and apoptosiswere 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 overexpressionor curcumin treatment.
Results: Curcumin caused a significant and dose-dependent increase of miR-9 expressionin SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled withreduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavageof caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blotanalysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) declinein the phosphorylation of Akt and FOXO1, compared to untreated cells.
Conclusions: The present studyprovided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely throughupregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identifydirect targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.