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
Hauptverfasser: Ciolino, Henry P, Dai, Zhaoli, Nair, Vidhya
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creator Ciolino, Henry P
Dai, Zhaoli
Nair, Vidhya
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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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. 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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. 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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. 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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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