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Effect of resveratrol on the development of spontaneous mammary tumors in HER‐2/ neu transgenic mice
Author(s) -
Provinciali Mauro,
Re Francesca,
Donnini Alessia,
Orlando Fiorenza,
Bartozzi Beatrice,
Di Stasio Grazia,
Smorlesi Arianna
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20874
Subject(s) - genetically modified mouse , mammary tumor , apoptosis , in vivo , downregulation and upregulation , her2/neu , mammary gland , transgene , cancer research , skbr3 , biology , resveratrol , endocrinology , medicine , cancer , cancer cell , breast cancer , pharmacology , gene , biochemistry , human breast , microbiology and biotechnology
Resveratrol (Res) has been reported to possess cancer chemopreventive activity on the basis of its in vitro effects on tumor cells and in vivo experimental models of rodents transplanted with parental tumors or treated with carcinogens. We investigated the effects of Res on the development of mammary tumors appearing spontaneously in HER‐2/ neu transgenic mice at an early age. The mechanisms involved in the Res antitumor effect were evaluated by studying the immune effectiveness, tumor apoptosis and expression of mRNA and protein for HER‐2/ neu in tumoral mammary glands from Res‐treated mice and in tumor cell lines. Res supplementation delayed the development of spontaneous mammary tumors ( p < 0.001), reduced the mean number and size of mammary tumors ( p < 0.0001) and diminished the number of lung metastases in HER‐2/ neu transgenic mice. The effects of Res were associated with downregulation of HER‐2/neu gene expression and increased apoptosis both in tumoral mammary glands and in murine (N202) and human (SKBr3) tumor cell lines. Neither the basal, the IL‐2‐induced NK activity nor the lymphocyte number and proliferation was modified in Res‐supplemented compared to control mice. Our results demonstrate that Res supplementation delays the development and reduces the metastasizing capacity of spontaneous mammary tumors in HER‐2/ neu transgenic mice. The antitumor effect of Res might be related to the downregulation of HER‐2/ neu expression and the induction of apoptosis in tumor cells. © 2005 Wiley‐Liss, Inc.