Forkhead proteins are critical for bone morphogenetic protein-2 regulation and anti-tumor activity of resveratrol
Journal
Journal of Biological Chemistry
Journal Volume
282
Journal Issue
27
Pages
19385-19398
Date Issued
2007
Author(s)
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. ? 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
SDGs
Other Subjects
Bone; Enzyme activity; Enzyme kinetics; Health care; Hormones; Tumors; Anti-tumor activity; Bone morphogenetic protein; Public health; Resveratrol; Proteins; 4 amino 7 tert butyl 5 (4 methylphenyl)pyrazolo[3,4 d]pyrimidine; bone morphogenetic protein 2; estradiol; estrogen receptor; forkhead transcription factor; hepatocyte nuclear factor 3alpha; osteocalcin; osteopontin; protein kinase B; resveratrol; transcription factor FKHRL1; animal cell; animal experiment; animal model; animal tissue; antineoplastic activity; article; bone; bone development; breast cancer; cancer inhibition; cancer risk; cell nucleus; concentration response; controlled study; dual energy X ray absorptiometry; female; hormone substitution; human; human cell; in vitro study; in vivo study; intermethod comparison; mouse; nonhuman; osteolysis; ovariectomy; postmenopause osteoporosis; priority journal; protection; protein expression; protein function; protein induction; rat; receptor upregulation; regulatory mechanism; risk reduction; tumor growth; Animals; Antineoplastic Agents, Phytogenic; Bone Morphogenetic Proteins; Breast Neoplasms; Cell Line, Tumor; Estrogen Replacement Therapy; Estrogens; Female; Forkhead Transcription Factors; Gene Expression Regulation, Enzymologic; Humans; Mice; Osteoporosis, Postmenopausal; Proto-Oncogene Proteins c-akt; Receptors, Estrogen; Risk Factors; src-Family Kinases; Stilbenes; Transforming Growth Factor beta
Type
journal article