title: Induction of microRNA-9 mediates cytotoxicity of curcumin against SKOV3 ovarian cancer cells.
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.
  
  
  METHODS
  SKOV3 ovarian cancer cells were treated with curcumin (10-60 μM) 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.
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China E-mail : Songf_zhao_2013@163.com.
authors.forename: Song-Feng
authors.initials: SF
authors.lastname: Zhao
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Xiu-Qin
authors.initials: XQ
authors.lastname: Shi
authors.forename: Zu-Jiang
authors.initials: ZJ
authors.lastname: Yu
authors.forename: Quan-Cheng
authors.initials: QC
authors.lastname: Kan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010051:Ovarian Neoplasms; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D000970:Antineoplastic Agents; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin