Dietary grape polyphenol resveratrol increases mammary tumor growth and metastasis in immunocompromised mice

BMC Complementary and Alternative Medicine

Research Article

Luis A Cubano¹  Suranganie Dharmawardhane²  Linette Castillo-Pichardo³ 

[1] Department of Anatomy and Cell Biology, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico;Department of Biochemistry, School of Medicine, University of Puerto Rico, PO Box 365067, Medical Sciences Campus, San Juan, Puerto Rico;Department of Biochemistry, School of Medicine, University of Puerto Rico, PO Box 365067, Medical Sciences Campus, San Juan, Puerto Rico;Department of Pathology and Laboratory Medicine, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico;

关键词: Breast cancer;    Resveratrol;    Metastasis;    Grape polyphenols;    Rac;   

DOI  :  10.1186/1472-6882-13-6

 received in 2012-07-20, accepted in 2013-01-02,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundResveratrol, a polyphenol from grapes and red wine has many health beneficial effects, including protection against cardiovascular and neurodegenerative diseases and cancer. However, our group and others have provided evidence for a dual cancer promoting or inhibitory role for resveratrol in breast cancer, dependent on estrogenic or antiestrogenic activities. Moreover, much of the inhibitory effects of resveratrol have been reported from studies with high non-physiological concentrations.MethodsWe investigated the effects of a range of concentrations (0.5, 5, 50 mg/kg body weight) of resveratrol on mammary tumor development post-initiation, using immunocompromised mice.ResultsOur findings suggest promotion of mammary tumor growth and metastasis by resveratrol at all concentrations tested in tumors derived from the low metastatic estrogen receptor (ER)α(-), ERβ(+) MDA-MB-231 and the highly metastatic ER(-) MDA-MB-435 cancer cell lines. Additionally, the activity of the migration/invasion regulator Rac, which we have previously shown to be regulated by resveratrol in vitro, was measured in tumors from resveratrol treated mice. Our results show a significant induction of tumoral Rac activity and a trend in increased expression of the Rac downstream effector PAK1 and other tumor promoting molecules following resveratrol treatment.ConclusionTaken together, our findings implicate low concentrations of resveratrol in potential promotion of breast cancer. Therefore, this study illuminates the importance of further delineating resveratrol’s concentration dependent effects, particularly in breast cancer, before it can be tested in the clinic or used as a dietary supplement for breast cancer patients.

【 授权许可】

Unknown   
© Castillo-Pichardo et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.