title: Curcumin attenuates EGF-induced AQP3 up-regulation and cell migration in human ovarian cancer cells.
abstract: OBJECTIVE
  Aquaporin (AQP) water channels are expressed in high-grade tumor cells of different tissue origins. Based on the involvement of AQPs in angiogenesis and cell migration as well as our previous studies which show that AQP3 is involved in human skin fibroblasts cell migration, in this study, we investigated whether AQP3 is expressed in cultured human ovarian cancer cell line CaOV3 cells, and whether AQP3 expression in these cells enhances cell migration and metastatic potential.
  
  
  METHODS
  Cultured CaOV3 cells were treated with EGF and/or various reagents and subjected to cell migration assay by phagokinetic track mobility assay or biochemical analysis for expression or activation of proteins by SDS-PAGE/Western blot analysis.
  
  
  RESULTS
  In this study, we demonstrate that AQP3 is expressed in CaOV3 cells. EGF induces CaOV3 migration and up-regulates AQP3 expression. EGF-induced cell migration is inhibited by specific AQP3 siRNA knockdown or AQP3 water transport inhibitor CuSO4 and NiCl2. We also find that curcumin, a well known anti-ovarian cancer drug, down-regulates AQP3 expression and reduces cell migration in CaOV3, and the effects of curcumin are mediated, at least in part, by its inhibitory effects on EGFR and downstream AKT/ERK activation.
  
  
  CONCLUSIONS
  Collectively, our results provide evidence for AQP3-facilitated ovarian cancer cell migration, suggesting a novel function for AQP3 expression in high-grade tumors. The results that curcumin inhibits EGF-induced up-regulation of AQP3 and cell migration, provide a new explanation for the anticancer potential of curcumin.
authors.affiliation: Department of Biology, Providence College, 549 River Ave, Providence, RI 02918, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Ji
authors.forename: Cong
authors.initials: C
authors.lastname: Cao
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kivlin
authors.forename: Ashley
authors.initials: A
authors.lastname: Amaral
authors.forename: Nicola
authors.initials: N
authors.lastname: Kouttab
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Wenming
authors.initials: W
authors.lastname: Chu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Bi
authors.forename: Wen
authors.initials: W
authors.lastname: Di
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D051400:Aquaporin 3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D019327:Copper Sulfate / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D009532:Nickel / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034622:RNA Interference; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051400:Aquaporin 3; D004815:Epidermal Growth Factor; C022838:nickel chloride; D009532:Nickel; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D003474:Curcumin; D019327:Copper Sulfate