Effects of conformationally restricted synthetic retinoids on ovarian tumor cell growth
We have used conformationally restricted retinoids to investigate the role of individual RAR subtypes and RXR in mediating the growth response of ovarian tumor cells to retinoids. Our results show that treatment of all‐trans‐RA‐sensitive CAOV‐3 cells with retinoids that bind and activate a single RA...
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| Veröffentlicht in: | Journal of cellular biochemistry 1998-03, Vol.68 (3), p.378-388 |
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| creator | Wu, Shujian Zhang, Dongmei Donigan, Anne Dawson, Marcia I. Soprano, Dianne Robert Soprano, Kenneth J. |
| description | We have used conformationally restricted retinoids to investigate the role of individual RAR subtypes and RXR in mediating the growth response of ovarian tumor cells to retinoids. Our results show that treatment of all‐trans‐RA‐sensitive CAOV‐3 cells with retinoids that bind and activate a single RAR or RXR led to a partial inhibition of growth. Treatment of all‐trans‐RA‐ resistant SKOV‐3 cells did not alter growth. Maximum inhibition of growth, comparable to that observed following treatment with natural retinoids such as all‐trans‐RA and 9‐cis‐RA, was obtained only following treatment with a combination of an RAR‐selective compound and an RXR‐selective one. These results suggest that activation of both RAR and RXR classes is required in order to obtain maximum inhibition of ovarian tumor cell growth by retinoids. In addition, one compound, AHPN, was found to inhibit both RA‐sensitive CAOV‐3 and RA‐resistant SKOV‐3 cells. Further study of the effects of this retinoid showed that AHPN acts through an apoptotic pathway. Taken together, our results suggest that retinoids may serve as effective anti‐proliferative agents in the treatment of ovarian cancer. J. Cell. Biochem. 68:378–388, 1998. © 1998 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/(SICI)1097-4644(19980301)68:3<378::AID-JCB8>3.0.CO;2-R |
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Our results show that treatment of all‐trans‐RA‐sensitive CAOV‐3 cells with retinoids that bind and activate a single RAR or RXR led to a partial inhibition of growth. Treatment of all‐trans‐RA‐ resistant SKOV‐3 cells did not alter growth. Maximum inhibition of growth, comparable to that observed following treatment with natural retinoids such as all‐trans‐RA and 9‐cis‐RA, was obtained only following treatment with a combination of an RAR‐selective compound and an RXR‐selective one. These results suggest that activation of both RAR and RXR classes is required in order to obtain maximum inhibition of ovarian tumor cell growth by retinoids. In addition, one compound, AHPN, was found to inhibit both RA‐sensitive CAOV‐3 and RA‐resistant SKOV‐3 cells. Further study of the effects of this retinoid showed that AHPN acts through an apoptotic pathway. Taken together, our results suggest that retinoids may serve as effective anti‐proliferative agents in the treatment of ovarian cancer. J. Cell. Biochem. 68:378–388, 1998. © 1998 Wiley‐Liss, Inc.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/(SICI)1097-4644(19980301)68:3<378::AID-JCB8>3.0.CO;2-R</identifier><identifier>PMID: 9518263</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>AHPN ; apoptosis ; Apoptosis - drug effects ; Cell Transformation, Neoplastic - drug effects ; Dose-Response Relationship, Drug ; Female ; growth suppression ; Humans ; Ligands ; Molecular Conformation ; ovarian cancer ; Ovarian Neoplasms - pathology ; Receptors, Retinoic Acid ; retinoic acid receptors ; Retinoid X Receptors ; Retinoids - administration & dosage ; Retinoids - chemistry ; Retinoids - pharmacology ; Structure-Activity Relationship ; Time Factors ; Transcription Factors ; Tumor Cells, Cultured</subject><ispartof>Journal of cellular biochemistry, 1998-03, Vol.68 (3), p.378-388</ispartof><rights>Copyright © 1998 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4028-7d2fad681ac7246cd59e84486948fe755795839875ec0ac51f0fc32b580490093</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2F%28SICI%291097-4644%2819980301%2968%3A3%3C378%3A%3AAID-JCB8%3E3.0.CO%3B2-R$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2F%28SICI%291097-4644%2819980301%2968%3A3%3C378%3A%3AAID-JCB8%3E3.0.CO%3B2-R$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9518263$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Shujian</creatorcontrib><creatorcontrib>Zhang, Dongmei</creatorcontrib><creatorcontrib>Donigan, Anne</creatorcontrib><creatorcontrib>Dawson, Marcia I.</creatorcontrib><creatorcontrib>Soprano, Dianne Robert</creatorcontrib><creatorcontrib>Soprano, Kenneth J.</creatorcontrib><title>Effects of conformationally restricted synthetic retinoids on ovarian tumor cell growth</title><title>Journal of cellular biochemistry</title><addtitle>J. Cell. Biochem</addtitle><description>We have used conformationally restricted retinoids to investigate the role of individual RAR subtypes and RXR in mediating the growth response of ovarian tumor cells to retinoids. Our results show that treatment of all‐trans‐RA‐sensitive CAOV‐3 cells with retinoids that bind and activate a single RAR or RXR led to a partial inhibition of growth. Treatment of all‐trans‐RA‐ resistant SKOV‐3 cells did not alter growth. Maximum inhibition of growth, comparable to that observed following treatment with natural retinoids such as all‐trans‐RA and 9‐cis‐RA, was obtained only following treatment with a combination of an RAR‐selective compound and an RXR‐selective one. These results suggest that activation of both RAR and RXR classes is required in order to obtain maximum inhibition of ovarian tumor cell growth by retinoids. In addition, one compound, AHPN, was found to inhibit both RA‐sensitive CAOV‐3 and RA‐resistant SKOV‐3 cells. Further study of the effects of this retinoid showed that AHPN acts through an apoptotic pathway. Taken together, our results suggest that retinoids may serve as effective anti‐proliferative agents in the treatment of ovarian cancer. J. Cell. Biochem. 68:378–388, 1998. © 1998 Wiley‐Liss, Inc.</description><subject>AHPN</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Cell Transformation, Neoplastic - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>growth suppression</subject><subject>Humans</subject><subject>Ligands</subject><subject>Molecular Conformation</subject><subject>ovarian cancer</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Receptors, Retinoic Acid</subject><subject>retinoic acid receptors</subject><subject>Retinoid X Receptors</subject><subject>Retinoids - administration & dosage</subject><subject>Retinoids - chemistry</subject><subject>Retinoids - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Time Factors</subject><subject>Transcription Factors</subject><subject>Tumor Cells, Cultured</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1vEzEQhlcIVELhJyDtCbWHDf5Yr-2AKpVt0waVBpWPHkeu16Yum3VrOy359-ySEA4gcbLGmnnemSfLDjAaY4TI671Ps3q2j5HkRVmV5R6WUiCK8H4lJvQt5WIyOZwdFe_rd-KAjtG4nr8hxcWjbLQdeZyNEKeoIBSTp9mzGG8QQlJSspPtSIYFqegouzy21ugUc29z7Tvrw0Il5zvVtqs8mJiC08k0eVx16dokp_vP5Drvmn6ky_29Ck51eVoufMi1adv8W_AP6fp59sSqNpoXm3c3-zI9_lyfFmfzk1l9eFboEhFR8IZY1VQCK81JWemGSSPKUlSyFNZwxrhkgkrBmdFIaYYtspqSKyZQKftr6G72as29Df5u2e8LCxeHPVRn_DIClxwxRnHf-HXdqIOPMRgLt8EtVFgBRjAYBxiMw6APBn3w2zhUAij0xgF64zAY72sE9RwIXPTgl5sNllcL02yxG8V_gh9ca1Z_pf439B-Zv-oeXKzBLibzYwtW4TtUnHIGl-cnwKf0w_nRx1OY0p9Sm6tM</recordid><startdate>19980301</startdate><enddate>19980301</enddate><creator>Wu, Shujian</creator><creator>Zhang, Dongmei</creator><creator>Donigan, Anne</creator><creator>Dawson, Marcia I.</creator><creator>Soprano, Dianne Robert</creator><creator>Soprano, Kenneth J.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>19980301</creationdate><title>Effects of conformationally restricted synthetic retinoids on ovarian tumor cell growth</title><author>Wu, Shujian ; Zhang, Dongmei ; Donigan, Anne ; Dawson, Marcia I. ; Soprano, Dianne Robert ; Soprano, Kenneth J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4028-7d2fad681ac7246cd59e84486948fe755795839875ec0ac51f0fc32b580490093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>AHPN</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Cell Transformation, Neoplastic - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>growth suppression</topic><topic>Humans</topic><topic>Ligands</topic><topic>Molecular Conformation</topic><topic>ovarian cancer</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Receptors, Retinoic Acid</topic><topic>retinoic acid receptors</topic><topic>Retinoid X Receptors</topic><topic>Retinoids - administration & dosage</topic><topic>Retinoids - chemistry</topic><topic>Retinoids - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>Time Factors</topic><topic>Transcription Factors</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Shujian</creatorcontrib><creatorcontrib>Zhang, Dongmei</creatorcontrib><creatorcontrib>Donigan, Anne</creatorcontrib><creatorcontrib>Dawson, Marcia I.</creatorcontrib><creatorcontrib>Soprano, Dianne Robert</creatorcontrib><creatorcontrib>Soprano, Kenneth J.</creatorcontrib><collection>Istex</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>Journal of cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Shujian</au><au>Zhang, Dongmei</au><au>Donigan, Anne</au><au>Dawson, Marcia I.</au><au>Soprano, Dianne Robert</au><au>Soprano, Kenneth J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of conformationally restricted synthetic retinoids on ovarian tumor cell growth</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J. Cell. Biochem</addtitle><date>1998-03-01</date><risdate>1998</risdate><volume>68</volume><issue>3</issue><spage>378</spage><epage>388</epage><pages>378-388</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><abstract>We have used conformationally restricted retinoids to investigate the role of individual RAR subtypes and RXR in mediating the growth response of ovarian tumor cells to retinoids. Our results show that treatment of all‐trans‐RA‐sensitive CAOV‐3 cells with retinoids that bind and activate a single RAR or RXR led to a partial inhibition of growth. Treatment of all‐trans‐RA‐ resistant SKOV‐3 cells did not alter growth. Maximum inhibition of growth, comparable to that observed following treatment with natural retinoids such as all‐trans‐RA and 9‐cis‐RA, was obtained only following treatment with a combination of an RAR‐selective compound and an RXR‐selective one. These results suggest that activation of both RAR and RXR classes is required in order to obtain maximum inhibition of ovarian tumor cell growth by retinoids. In addition, one compound, AHPN, was found to inhibit both RA‐sensitive CAOV‐3 and RA‐resistant SKOV‐3 cells. Further study of the effects of this retinoid showed that AHPN acts through an apoptotic pathway. Taken together, our results suggest that retinoids may serve as effective anti‐proliferative agents in the treatment of ovarian cancer. J. Cell. Biochem. 68:378–388, 1998. © 1998 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>9518263</pmid><doi>10.1002/(SICI)1097-4644(19980301)68:3<378::AID-JCB8>3.0.CO;2-R</doi><tpages>11</tpages></addata></record> |
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| subjects | AHPN apoptosis Apoptosis - drug effects Cell Transformation, Neoplastic - drug effects Dose-Response Relationship, Drug Female growth suppression Humans Ligands Molecular Conformation ovarian cancer Ovarian Neoplasms - pathology Receptors, Retinoic Acid retinoic acid receptors Retinoid X Receptors Retinoids - administration & dosage Retinoids - chemistry Retinoids - pharmacology Structure-Activity Relationship Time Factors Transcription Factors Tumor Cells, Cultured |
| title | Effects of conformationally restricted synthetic retinoids on ovarian tumor cell growth |
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