Su Jen-Liang, Yang Ching-Yao, Zhao Ming, Kuo Min-Liang, Yen Men-Luh
Graduate Institute of Cancer Biology, College of Medicine, China Medical University, Taichung 404, Taiwan.
J Biol Chem. 2007 Jul 6;282(27):19385-98. doi: 10.1074/jbc.M702452200. Epub 2007 May 18.
Osteoporosis is a major public health problem and the most obvious preventive strategy, hormone replacement therapy, has lost favor due to recent findings of the Women's Health Initiative regarding increased risks of breast cancer and cardiovascular disease. Resveratrol, a naturally occurring compound possessing estrogenic activity, is thought to have considerable potential for therapy of osteoporosis. In the present study, resveratrol was found to exhibit bone-protective effects equivalent to those exerted by hormone replacement therapy and decrease the risk of breast cancer in the in vivo and in vitro models. Forkhead proteins were found to be essential for both effects of resveratrol. The bone-protective effect was attributable to induction of bone morphogenetic protein-2 through Src kinase-dependent estrogen receptor activation and FOXA1 is required for resveratrol-induced estrogen receptor-dependent bone morphogenetic protein-2 expression. The tumor-suppressive effects of resveratrol were the consequence of Akt inactivation-mediated FOXO3a nuclear accumulation and activation. Resveratrol is therefore anticipated to be highly effective in management of postmenopausal osteoporosis without an increased risk of breast cancer.
骨质疏松症是一个重大的公共卫生问题，而最明显的预防策略——激素替代疗法，由于妇女健康倡议组织最近发现其会增加乳腺癌和心血管疾病风险而失宠。白藜芦醇是一种具有雌激素活性的天然化合物，被认为在骨质疏松症治疗方面具有相当大的潜力。在本研究中，发现白藜芦醇在体内和体外模型中均表现出与激素替代疗法相当的骨保护作用，并降低了乳腺癌风险。发现叉头蛋白对白藜芦醇的这两种作用都至关重要。骨保护作用归因于通过Src激酶依赖性雌激素受体激活诱导骨形态发生蛋白-2，而FOXA1是白藜芦醇诱导雌激素受体依赖性骨形态发生蛋白-2表达所必需的。白藜芦醇的肿瘤抑制作用是Akt失活介导的FOXO3a核积累和激活的结果。因此，预计白藜芦醇在治疗绝经后骨质疏松症方面非常有效，且不会增加乳腺癌风险。
