Journal
ONCOLOGY REPORTS
Volume 25, Issue 6, Pages 1713-1719Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2011.1248
Keywords
resveratrol; apoptosis stimulation protein of p53; apoptosis; E2F-1; MDA-MB231; MCF-7; breast cancer
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Funding
- American Cancer Society (ACS)
- Oklahoma Center for the Advancement of Science and Technology (OCAST)
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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 ASPP I may represent a novel therapeutic target for resveratrol in human breast cancer.
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