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Resveratrol is a natural polyphenolic compound with cancer chemopreventive activity. However, our understanding of the molecular mechanism responsible for resveratrol-induced apoptosis is still very limited. Here, we used MCF-7 and MDA-MB231 breast cancer cells as a model to demonstrate that resveratrol induced the expression of ASPP1, a new member of the ASPP (apoptosis stimulation protein of p53) family, which plays an important role in the regulation of apoptosis. Moreover, resveratrol enhanced apoptosis of MCF-7/ASPP1 cells, accompanied by higher expression of bax and p21. In contrast, siRNA-mediated knockdown of ASPP1 inhibited apoptosis in MB231 cells. Furthermore, we found that higher levels of ASPP1 were associated with adenovirus-mediated overexpression of E2F1 while siRNA-mediated E2F1 knockdown led to down-regulation of ASPP1. In conclusion, our results demonstrate that overexpression of ASPP1 rendered MCF-7 and MDA-MB231 breast cancer cells more sensitive to resveratrol-mediated apoptosis via the E2F pathway, thus suggesting that ASPP1 may represent a novel therapeutic target for resveratrol in human breast cancer.

Original publication

DOI

10.3892/or.2011.1248

Type

Journal article

Journal

Oncol Rep

Publication Date

06/2011

Volume

25

Pages

1713 - 1719

Keywords

Adaptor Proteins, Signal Transducing, Antineoplastic Agents, Phytogenic, Apoptosis, Apoptosis Regulatory Proteins, Blotting, Western, Breast Neoplasms, Cell Line, Tumor, E2F1 Transcription Factor, Female, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Stilbenes, Transfection, Up-Regulation