Curcumin attenuates EGF-induced AQP3 up-regulation and cell migration in human ovarian cancer cells.
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.
Ji
Chao
C
Department of Biology, Providence College, 549 River Ave, Providence, RI 02918, USA.
Cao
Cong
C
Lu
Shan
S
Kivlin
Rebecca
R
Amaral
Ashley
A
Kouttab
Nicola
N
Yang
Hui
H
Chu
Wenming
W
Bi
Zhigang
Z
Di
Wen
W
Wan
Yinsheng
Y
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
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