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- Title
Induction of Apoptosis and Cell Cycle Arrest in Human Breast Cancer Cells, MCF-7, by Adiponectin.
- Authors
Li Cong; Gasser, Jessica; Ke Chen; Zhao, Jessica; Zhao, Allan
- Abstract
Obesity is a well-known risk factor for breast cancer in postmenopausal women. Multiple fat-derived factors may have contributed to the pathogenesis of breast cancer. Recent clinical studies have demonstrated that low blood concentrations of adiponectin are associated with high incidence and poor prognosis of breast cancer. This study investigated the inhibitory effects of adiponectin on a human breast cancer cell line, MCF-7, and addressed the potential mechanism(s) underlying the effects of adiponectin. MCF-7 cells were serum starved before treated with human adiponectin (20 and 40 µg/ml) and/or IGF-1 (10 ng/ml) for 48- or 96-hr. We determined the percentage of cells at different stages of cell cycle and apoptotic cells using FACS. We also monitored the activities of AMPK, c-akt, and mitogen-activated protein kinase (MAPK, p42/44), as well as the expression of cyclin D1 and cyclin E2. Through counting the cells, we found that adiponectin treatment significantly reduced cell growth at 48- and 96-hr. Adiponectin also suppressed IGF-1-induced cell proliferation. These inhibitory effects were primarily due to cell cycle arrest at G1/G0 phase. In addition, the percentage of apoptotic cells increased more than 2-fold. Within 30-min of adiponectin treatment, the phosphorylation of AMPKα (Thr172) was drastically elevated. Pro-longed exposure (48 hr) of the cells to adiponectin resulted in reduction of cyclin D1 and cyclin E2 expression. During the 48-hour treatment, adiponectin also decreased the activity of MAPK (p42/44) (reflected in the phosphorylation at Thr202/Tyr204), while having no effect on the activity of c-akt. In conclusion, human adiponectin opposes the growth (and IGF-1-stimulated growth) of the cultured human breast cancer MCF-7 cells by inducing cell cycle arrest and apoptosis. Such negative effects appear to be mediated through reduction of cyclin D1 and cyclin E2 expression as well as through reduction of IGF-1-induced MAPK. These observations may help explain in part the increased risk of breast cancer in obese women. ADA-Funded Research
- Publication
Diabetes, 2007, Vol 56, pA509
- ISSN
0012-1797
- Publication type
Academic Journal