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Published on: March 15, 2018
Forkhead proteins are critical for bone morphogenetic protein-2 regulation and anti-tumor activity of resveratrol
Jen-Liang Su1, Ching-Yao Yang, Ming Zhao
1Graduate Institute of Cancer Biology, College of Medicine, China Medical University, Taichung 404, Taiwan.
Abstract:
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.
Insights
Resveratrol shows promise for treating osteoporosis by protecting bones and reducing breast cancer risk, similar to hormone replacement therapy but without the associated dangers. This natural compound offers a safer alternative for postmenopausal women.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Osteoporosis is a significant public health concern, with hormone replacement therapy (HRT) facing reduced use due to safety concerns like increased breast cancer and cardiovascular risks.
- Resveratrol, a natural compound with estrogenic properties, presents a potential therapeutic agent for osteoporosis.
Purpose of the Study:
- To evaluate the efficacy of resveratrol in preventing bone loss and reducing breast cancer risk.
- To elucidate the molecular mechanisms underlying resveratrol's bone-protective and tumor-suppressive effects, focusing on forkhead proteins.
Main Methods:
- In vivo and in vitro studies were conducted to assess resveratrol's effects on bone health and cancer risk.
- Molecular analyses investigated the roles of forkhead proteins (FOXA1, FOXO3a), Src kinase, estrogen receptors, and Akt signaling pathways.
Main Results:
- Resveratrol demonstrated bone-protective effects comparable to HRT.
- Resveratrol reduced the risk of breast cancer in experimental models.
- The bone-protective effect involved the induction of bone morphogenetic protein-2 via estrogen receptor activation, with FOXA1 being crucial.
- Tumor-suppressive effects were linked to Akt inactivation and subsequent FOXO3a nuclear accumulation.
Conclusions:
- Resveratrol offers a potentially effective and safer therapeutic strategy for postmenopausal osteoporosis management.
- Resveratrol may mitigate osteoporosis without increasing breast cancer risk, mediated by forkhead protein pathways.
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