Retinol inhibits aromatase activity and expression in vitro
Aromatase converts androgens into estrogens and is thought to supply a local source of estrogen that facilitates the growth of hormone-responsive tumor cells. Inhibition of aromatase is therefore an important chemopreventive strategy. We investigated the effect of retinol and selected retinoids on t...
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Veröffentlicht in: | The Journal of nutritional biochemistry 2011-06, Vol.22 (6), p.522-526 |
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description | Aromatase converts androgens into estrogens and is thought to supply a local source of estrogen that facilitates the growth of hormone-responsive tumor cells. Inhibition of aromatase is therefore an important chemopreventive strategy. We investigated the effect of retinol and selected retinoids on the activity and expression of aromatase in two human carcinoma cell lines in vitro. Retinol (ROH) and all-trans retinoic acid (ATRA) significantly inhibited aromatase activity in a concentration-dependent manner in microsomes isolated from JEG-3 human placental carcinoma cells, whereas 9-cis and 13-cis retinoic acid had significant inhibitory activity only at the highest concentrations tested. Similar results were observed in an assay of cellular aromatase activity in MCF-7 human breast cancer cells. Enzyme kinetic studies by double-reciprocal plot demonstrated that ROH inhibited microsomal aromatase activity in a mixed manner. In addition, ROH suppressed both the basal and cAMP-induced expression of aromatase mRNA in MCF-7 cells and inhibited transcription controlled by a cAMP-responsive element. These results suggest that aromatase activity and expression are a molecular target of ROH and chemopreventive retinoids, an activity that may underlie, in part, their inhibitory effects on hormone-dependent cancer. |
doi_str_mv | 10.1016/j.jnutbio.2010.04.004 |
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Inhibition of aromatase is therefore an important chemopreventive strategy. We investigated the effect of retinol and selected retinoids on the activity and expression of aromatase in two human carcinoma cell lines in vitro. Retinol (ROH) and all-trans retinoic acid (ATRA) significantly inhibited aromatase activity in a concentration-dependent manner in microsomes isolated from JEG-3 human placental carcinoma cells, whereas 9-cis and 13-cis retinoic acid had significant inhibitory activity only at the highest concentrations tested. Similar results were observed in an assay of cellular aromatase activity in MCF-7 human breast cancer cells. Enzyme kinetic studies by double-reciprocal plot demonstrated that ROH inhibited microsomal aromatase activity in a mixed manner. In addition, ROH suppressed both the basal and cAMP-induced expression of aromatase mRNA in MCF-7 cells and inhibited transcription controlled by a cAMP-responsive element. These results suggest that aromatase activity and expression are a molecular target of ROH and chemopreventive retinoids, an activity that may underlie, in part, their inhibitory effects on hormone-dependent cancer.</description><identifier>ISSN: 0955-2863</identifier><identifier>EISSN: 1873-4847</identifier><identifier>DOI: 10.1016/j.jnutbio.2010.04.004</identifier><identifier>PMID: 20685100</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>androgens ; Aromatase ; Aromatase - metabolism ; Biological and medical sciences ; breast neoplasms ; Breast Neoplasms - metabolism ; cAMP ; carcinoma ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; estrogens ; Feeding. Feeding behavior ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Neoplastic ; Humans ; Kinetics ; MCF-7 cells ; messenger RNA ; microsomes ; Retinoic acid ; Retinol ; RNA, Messenger - metabolism ; Tretinoin - pharmacology ; unspecific monooxygenase ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; vitamin A ; Vitamin A - pharmacology ; Vitamins</subject><ispartof>The Journal of nutritional biochemistry, 2011-06, Vol.22 (6), p.522-526</ispartof><rights>2011 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-eaf0eb5f148c214cb376ee8daf532983d947cb2e81f4c18217bca5878205c9153</citedby><cites>FETCH-LOGICAL-c442t-eaf0eb5f148c214cb376ee8daf532983d947cb2e81f4c18217bca5878205c9153</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jnutbio.2010.04.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24198760$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20685100$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ciolino, Henry P</creatorcontrib><creatorcontrib>Dai, Zhaoli</creatorcontrib><creatorcontrib>Nair, Vidhya</creatorcontrib><title>Retinol inhibits aromatase activity and expression in vitro</title><title>The Journal of nutritional biochemistry</title><addtitle>J Nutr Biochem</addtitle><description>Aromatase converts androgens into estrogens and is thought to supply a local source of estrogen that facilitates the growth of hormone-responsive tumor cells. Inhibition of aromatase is therefore an important chemopreventive strategy. We investigated the effect of retinol and selected retinoids on the activity and expression of aromatase in two human carcinoma cell lines in vitro. Retinol (ROH) and all-trans retinoic acid (ATRA) significantly inhibited aromatase activity in a concentration-dependent manner in microsomes isolated from JEG-3 human placental carcinoma cells, whereas 9-cis and 13-cis retinoic acid had significant inhibitory activity only at the highest concentrations tested. Similar results were observed in an assay of cellular aromatase activity in MCF-7 human breast cancer cells. Enzyme kinetic studies by double-reciprocal plot demonstrated that ROH inhibited microsomal aromatase activity in a mixed manner. In addition, ROH suppressed both the basal and cAMP-induced expression of aromatase mRNA in MCF-7 cells and inhibited transcription controlled by a cAMP-responsive element. These results suggest that aromatase activity and expression are a molecular target of ROH and chemopreventive retinoids, an activity that may underlie, in part, their inhibitory effects on hormone-dependent cancer.</description><subject>androgens</subject><subject>Aromatase</subject><subject>Aromatase - metabolism</subject><subject>Biological and medical sciences</subject><subject>breast neoplasms</subject><subject>Breast Neoplasms - metabolism</subject><subject>cAMP</subject><subject>carcinoma</subject><subject>Cell Line, Tumor</subject><subject>Dose-Response Relationship, Drug</subject><subject>estrogens</subject><subject>Feeding. Feeding behavior</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Kinetics</subject><subject>MCF-7 cells</subject><subject>messenger RNA</subject><subject>microsomes</subject><subject>Retinoic acid</subject><subject>Retinol</subject><subject>RNA, Messenger - metabolism</subject><subject>Tretinoin - pharmacology</subject><subject>unspecific monooxygenase</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>vitamin A</subject><subject>Vitamin A - pharmacology</subject><subject>Vitamins</subject><issn>0955-2863</issn><issn>1873-4847</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0E1rFDEYwPEgit1WP4J1LtLTrE_eM3goUmwrFAS155DJPGOzzE7WJFvstzfLbtubngLh9-TlT8g7CksKVH1cLVfztvQhLhnUPRBLAPGCLKjRvBVG6JdkAZ2ULTOKH5HjnFcAwIRUr8kRA2UkBViQT9-xhDlOTZjvQh9KblyKa1dcxsb5Eu5DeWjcPDT4Z5Mw5xDnSpu6neIb8mp0U8a3h_WE3F5--Xlx3d58u_p68fmm9UKw0qIbAXs5UmE8o8L3XCtEM7hRctYZPnRC-56hoaPw1DCqe--k0YaB9B2V_ISc7c_dpPh7i7nYdcgep8nNGLfZGqU541qqKuVe-hRzTjjaTQprlx4sBbvLZlf2kM3uslkQtmarc6eHG7b9GoenqcdOFXw4AJe9m8bkZh_ysxO0M1rt3Pu9G1207leq5vZHvUnU9pwrzf4pqBJ895jzvcDa9D5gstkHnD0OIaEvdojhP9_5CxE9n90</recordid><startdate>20110601</startdate><enddate>20110601</enddate><creator>Ciolino, Henry P</creator><creator>Dai, Zhaoli</creator><creator>Nair, Vidhya</creator><general>Elsevier Inc</general><general>New York, NY: Elsevier Science</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</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>7X8</scope></search><sort><creationdate>20110601</creationdate><title>Retinol inhibits aromatase activity and expression in vitro</title><author>Ciolino, Henry P ; Dai, Zhaoli ; Nair, Vidhya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-eaf0eb5f148c214cb376ee8daf532983d947cb2e81f4c18217bca5878205c9153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>androgens</topic><topic>Aromatase</topic><topic>Aromatase - metabolism</topic><topic>Biological and medical sciences</topic><topic>breast neoplasms</topic><topic>Breast Neoplasms - metabolism</topic><topic>cAMP</topic><topic>carcinoma</topic><topic>Cell Line, Tumor</topic><topic>Dose-Response Relationship, Drug</topic><topic>estrogens</topic><topic>Feeding. Feeding behavior</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Kinetics</topic><topic>MCF-7 cells</topic><topic>messenger RNA</topic><topic>microsomes</topic><topic>Retinoic acid</topic><topic>Retinol</topic><topic>RNA, Messenger - metabolism</topic><topic>Tretinoin - pharmacology</topic><topic>unspecific monooxygenase</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>vitamin A</topic><topic>Vitamin A - pharmacology</topic><topic>Vitamins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ciolino, Henry P</creatorcontrib><creatorcontrib>Dai, Zhaoli</creatorcontrib><creatorcontrib>Nair, Vidhya</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of nutritional biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ciolino, Henry P</au><au>Dai, Zhaoli</au><au>Nair, Vidhya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Retinol inhibits aromatase activity and expression in vitro</atitle><jtitle>The Journal of nutritional biochemistry</jtitle><addtitle>J Nutr Biochem</addtitle><date>2011-06-01</date><risdate>2011</risdate><volume>22</volume><issue>6</issue><spage>522</spage><epage>526</epage><pages>522-526</pages><issn>0955-2863</issn><eissn>1873-4847</eissn><abstract>Aromatase converts androgens into estrogens and is thought to supply a local source of estrogen that facilitates the growth of hormone-responsive tumor cells. Inhibition of aromatase is therefore an important chemopreventive strategy. We investigated the effect of retinol and selected retinoids on the activity and expression of aromatase in two human carcinoma cell lines in vitro. Retinol (ROH) and all-trans retinoic acid (ATRA) significantly inhibited aromatase activity in a concentration-dependent manner in microsomes isolated from JEG-3 human placental carcinoma cells, whereas 9-cis and 13-cis retinoic acid had significant inhibitory activity only at the highest concentrations tested. Similar results were observed in an assay of cellular aromatase activity in MCF-7 human breast cancer cells. Enzyme kinetic studies by double-reciprocal plot demonstrated that ROH inhibited microsomal aromatase activity in a mixed manner. In addition, ROH suppressed both the basal and cAMP-induced expression of aromatase mRNA in MCF-7 cells and inhibited transcription controlled by a cAMP-responsive element. These results suggest that aromatase activity and expression are a molecular target of ROH and chemopreventive retinoids, an activity that may underlie, in part, their inhibitory effects on hormone-dependent cancer.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>20685100</pmid><doi>10.1016/j.jnutbio.2010.04.004</doi><tpages>5</tpages></addata></record> |
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subjects | androgens Aromatase Aromatase - metabolism Biological and medical sciences breast neoplasms Breast Neoplasms - metabolism cAMP carcinoma Cell Line, Tumor Dose-Response Relationship, Drug estrogens Feeding. Feeding behavior Female Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Neoplastic Humans Kinetics MCF-7 cells messenger RNA microsomes Retinoic acid Retinol RNA, Messenger - metabolism Tretinoin - pharmacology unspecific monooxygenase Vertebrates: anatomy and physiology, studies on body, several organs or systems vitamin A Vitamin A - pharmacology Vitamins |
title | Retinol inhibits aromatase activity and expression in vitro |
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