A mechanism underlying the effects of polyunsaturated fatty acids on breast cancer

Zhang,Hao; Zhou,Lei; Shi,Wei; Song,Ning; Yu,Karu; Gu,Yuchun

doi:10.3892/ijmm.2012.1022

A mechanism underlying the effects of polyunsaturated fatty acids on breast cancer

Authors:
- Hao Zhang
- Lei Zhou
- Wei Shi
- Ning Song
- Karu Yu
- Yuchun Gu
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Affiliations: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, P.R. China, Department of Cardiology, Jiangsu General Hospital, Nanjing. P.R. China, Institute of Molecular Medicine, Peking University, Beijing, P.R. China
Published online on: June 11, 2012 https://doi.org/10.3892/ijmm.2012.1022
Pages: 487-494
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

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. Ca2+ entry was induced in these cells via activated TRPC3 by either the diacylglycerol analogue (OAG) or by intracellular Ca2+ store depletion. TRPC-mediated Ca2+ 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 Ca2+ entry. In addition, inhibition of COX2 reduced [Ca2+]i. Nevertheless, inhibition of TRPC reduced the cell cycle S phase and cell migration, implicating a functional role for TRP-mediated Ca2+ 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.

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