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Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and Anti-tumor Activity of Resveratrol
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 c...
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| Published in: | The Journal of biological chemistry 2007-07, Vol.282 (27), p.19385-19398 |
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| Main Authors: | , , , , |
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| cites | cdi_FETCH-LOGICAL-c442t-9cbf8c87f2c78ce30c5dfa01f92f5f08016c8eb2af3756085273cefae5ae40e3 |
| container_end_page | 19398 |
| container_issue | 27 |
| container_start_page | 19385 |
| container_title | The Journal of biological chemistry |
| container_volume | 282 |
| creator | Su, Jen-Liang Yang, Ching-Yao Zhao, Ming Kuo, Min-Liang Yen, Men-Luh |
| description | 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. |
| doi_str_mv | 10.1074/jbc.M702452200 |
| format | article |
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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.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M702452200</identifier><identifier>PMID: 17513867</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antineoplastic Agents, Phytogenic - pharmacology ; Antineoplastic Agents, Phytogenic - therapeutic use ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins - biosynthesis ; Breast Neoplasms - metabolism ; Cell Line, Tumor ; Estrogen Replacement Therapy ; Estrogens - pharmacology ; Estrogens - therapeutic use ; Female ; Forkhead Transcription Factors - metabolism ; Gene Expression Regulation, Enzymologic - drug effects ; Humans ; Mice ; Osteoporosis, Postmenopausal - drug therapy ; Osteoporosis, Postmenopausal - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; Receptors, Estrogen - agonists ; Receptors, Estrogen - metabolism ; Resveratrol ; Risk Factors ; src-Family Kinases - metabolism ; Stilbenes - pharmacology ; Stilbenes - therapeutic use ; Transforming Growth Factor beta - biosynthesis</subject><ispartof>The Journal of biological chemistry, 2007-07, Vol.282 (27), p.19385-19398</ispartof><rights>2007 © 2007 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-9cbf8c87f2c78ce30c5dfa01f92f5f08016c8eb2af3756085273cefae5ae40e3</citedby><cites>FETCH-LOGICAL-c442t-9cbf8c87f2c78ce30c5dfa01f92f5f08016c8eb2af3756085273cefae5ae40e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17513867$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Su, Jen-Liang</creatorcontrib><creatorcontrib>Yang, Ching-Yao</creatorcontrib><creatorcontrib>Zhao, Ming</creatorcontrib><creatorcontrib>Kuo, Min-Liang</creatorcontrib><creatorcontrib>Yen, Men-Luh</creatorcontrib><title>Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and Anti-tumor Activity of Resveratrol</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>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.</description><subject>Animals</subject><subject>Antineoplastic Agents, Phytogenic - pharmacology</subject><subject>Antineoplastic Agents, Phytogenic - therapeutic use</subject><subject>Bone Morphogenetic Protein 2</subject><subject>Bone Morphogenetic Proteins - biosynthesis</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Estrogen Replacement Therapy</subject><subject>Estrogens - pharmacology</subject><subject>Estrogens - therapeutic use</subject><subject>Female</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Humans</subject><subject>Mice</subject><subject>Osteoporosis, Postmenopausal - drug therapy</subject><subject>Osteoporosis, Postmenopausal - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptors, Estrogen - agonists</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Resveratrol</subject><subject>Risk Factors</subject><subject>src-Family Kinases - metabolism</subject><subject>Stilbenes - pharmacology</subject><subject>Stilbenes - therapeutic use</subject><subject>Transforming Growth Factor beta - biosynthesis</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNp1kD1v2zAQhomiReMkXTMGHIpucvkhmtToGkkTIEGLIkM3gqKOFlNJdEjKRf59GdhBpt5ywz3v3eFB6IKSJSWy_vrY2uW9JKwWjBHyDi0oUbzigv5-jxaEMFo1TKgTdJrSIylVN_QjOqFSUK5WcoGerkP804Pp8M8YMvgp4XUEvIk-e2sG7ELE38IE-D7EXR-2MEEZvMIVw79gOw8m-zBhM3V4PWVf5XkssbXNfu_zMw6uUGkP0eQYhnP0wZkhwadjP0MP11cPm5vq7sf32836rrJ1zXLV2NYpq6RjVioLnFjROUOoa5gTjihCV1ZBy4zjUqyIEkxyC86AMFAT4Gfoy2HtLoanGVLWo08WhsFMEOakaSMppStewOUBtDGkFMHpXfSjic-aEv3iWBfH-s1xCVweN8_tCN0bfpRagM8HoPfb_q-PoFsfbA-jZoppJsttrkTB1AGDYmHvIepkPUwWuhKxWXfB_--Ff1qnl_I</recordid><startdate>20070706</startdate><enddate>20070706</enddate><creator>Su, Jen-Liang</creator><creator>Yang, Ching-Yao</creator><creator>Zhao, Ming</creator><creator>Kuo, Min-Liang</creator><creator>Yen, Men-Luh</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope></search><sort><creationdate>20070706</creationdate><title>Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and Anti-tumor Activity of Resveratrol</title><author>Su, Jen-Liang ; Yang, Ching-Yao ; Zhao, Ming ; Kuo, Min-Liang ; Yen, Men-Luh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-9cbf8c87f2c78ce30c5dfa01f92f5f08016c8eb2af3756085273cefae5ae40e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Antineoplastic Agents, Phytogenic - pharmacology</topic><topic>Antineoplastic Agents, Phytogenic - therapeutic use</topic><topic>Bone Morphogenetic Protein 2</topic><topic>Bone Morphogenetic Proteins - biosynthesis</topic><topic>Breast Neoplasms - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Estrogen Replacement Therapy</topic><topic>Estrogens - pharmacology</topic><topic>Estrogens - therapeutic use</topic><topic>Female</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Humans</topic><topic>Mice</topic><topic>Osteoporosis, Postmenopausal - drug therapy</topic><topic>Osteoporosis, Postmenopausal - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptors, Estrogen - agonists</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Resveratrol</topic><topic>Risk Factors</topic><topic>src-Family Kinases - metabolism</topic><topic>Stilbenes - pharmacology</topic><topic>Stilbenes - therapeutic use</topic><topic>Transforming Growth Factor beta - biosynthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Su, Jen-Liang</creatorcontrib><creatorcontrib>Yang, Ching-Yao</creatorcontrib><creatorcontrib>Zhao, Ming</creatorcontrib><creatorcontrib>Kuo, Min-Liang</creatorcontrib><creatorcontrib>Yen, Men-Luh</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Su, Jen-Liang</au><au>Yang, Ching-Yao</au><au>Zhao, Ming</au><au>Kuo, Min-Liang</au><au>Yen, Men-Luh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and Anti-tumor Activity of Resveratrol</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2007-07-06</date><risdate>2007</risdate><volume>282</volume><issue>27</issue><spage>19385</spage><epage>19398</epage><pages>19385-19398</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>17513867</pmid><doi>10.1074/jbc.M702452200</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 2007-07, Vol.282 (27), p.19385-19398 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_19711163 |
| source | BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS; NCBI_PubMed Central（免费） |
| subjects | Animals Antineoplastic Agents, Phytogenic - pharmacology Antineoplastic Agents, Phytogenic - therapeutic use Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins - biosynthesis Breast Neoplasms - metabolism Cell Line, Tumor Estrogen Replacement Therapy Estrogens - pharmacology Estrogens - therapeutic use Female Forkhead Transcription Factors - metabolism Gene Expression Regulation, Enzymologic - drug effects Humans Mice Osteoporosis, Postmenopausal - drug therapy Osteoporosis, Postmenopausal - metabolism Proto-Oncogene Proteins c-akt - metabolism Receptors, Estrogen - agonists Receptors, Estrogen - metabolism Resveratrol Risk Factors src-Family Kinases - metabolism Stilbenes - pharmacology Stilbenes - therapeutic use Transforming Growth Factor beta - biosynthesis |
| title | Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and Anti-tumor Activity of Resveratrol |
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