A mechanism underlying the effects of polyunsaturated fatty acids on             breast cancer.
Breast cancer is the most frequent cancer in women. Evidence suggests that the polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) affect breast cancer proliferation, differentiation and prognosis. However, the mechanism still remains unclear. In this study, the expression of transient receptor potential canonical (TRPC)3 was detected throughout the cell cytoplasm and at the cell surface of MCF-7 cells. Ca(2+) entry was induced in these cells via activated TRPC3 by either the diacylglycerol analogue (OAG) or by intracellular Ca(2+) store depletion. TRPC-mediated Ca(2+) entry was inhibited by PUFAs including arachidonic acid (AA) and linolenic acid (LA) but not saturated fatty acids. Overexpression of the PUFA degradation enzyme, cyclooxygenase 2 (COX2), enhanced capacitative Ca(2+) entry. In addition, inhibition of COX2 reduced [Ca(2+)](i). Nevertheless, inhibition of TRPC reduced the cell cycle S phase and cell migration, implicating a functional role for TRP-mediated Ca(2+) entry in cell proliferation and invasion. Exogenous PUFA as well as a TRPC3 antagonist consistently attenuated breast cancer cell proliferation and migration, suggesting a mechanism in which PUFA restrains the breast cancer partly via its inhibition of TRPC channels. Additionally, our results also suggest that TRPC3 appears as a new mediator of breast cancer cell migration/invasion and represents a potential target for a new class of anticancer agent.
Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, P.R. China. ycgu@pku.edu.cn
Hao
H
Zhang
Lei
L
Zhou
Wei
W
Shi
Ning
N
Song
Karu
K
Yu
Yuchun
Y
Gu
D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D021122:Protein Subunits; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017962:alpha-Linolenic Acid / Q000494:pharmacology
C011439:1,2-diacylglycerol; D004075:Diglycerides; D005231:Fatty Acids, Unsaturated; D021122:Protein Subunits; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D017962:alpha-Linolenic Acid; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; D002118:Calcium