title: Resveratrol induces apoptosis in breast cancer cells by E2F1-mediated up-regulation of ASPP1.
abstract: 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.
authors.affiliation: Department of Physiology, College of Basic Medical Science, Zhengzhou University, Zhengzhou 450001, Henan, PR China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Shi
authors.forename: Shihe
authors.initials: S
authors.lastname: Yang
authors.forename: Sandi
authors.initials: S
authors.lastname: Troup
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Steve
authors.initials: S
authors.lastname: Callaghan
authors.forename: David S
authors.initials: DS
authors.lastname: Park
authors.forename: Ying
authors.initials: Y
authors.lastname: Xing
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D034741:RNA, Small Interfering; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D014162:Transfection; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C498406:PPP1R13B protein, human; D034741:RNA, Small Interfering; D013267:Stilbenes; D000077185:Resveratrol