Antiproliferative and Calcemic Actions of Trans-Decalin CD-Ring Analogs of 1,25-Dihydroxyvitamin D3
Background: 1,25-Dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] has potent antiproliferative actions but calcemic effects obstruct its application in the treatment of hyperproliferative disorders. Therefore, analogs of 1,25-(OH) 2 D 3 are designed with a clear dissociation between both effects. Here the bio...
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| Veröffentlicht in: | Anticancer research 2009-09, Vol.29 (9), p.3579-3584 |
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| container_title | Anticancer research |
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| creator | EELEN, Guy VERLINDEN, Lieve LAUREYS, Jos MARCELIS, Suzanne DE CLERCQ, Pierre MATHIEU, Chantal BOUILLON, Roger VERSTUYF, Annemieke |
| description | Background: 1,25-Dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] has potent antiproliferative actions but calcemic effects obstruct its application in the treatment of hyperproliferative
disorders. Therefore, analogs of 1,25-(OH) 2 D 3 are designed with a clear dissociation between both effects. Here the biological activity of the trans-decalin CD-ring analog
CY10012 is discussed. Materials and Methods: Proliferation/differentiation/transactivation assays as well as mouse models
were used to determine the activity of CY10012 in vitro and in vivo. Results: CY10012, has ten-fold higher antiproliferative
actions than 1,25(OH) 2 D 3 but is also twice as calcemic. To determine the role of the Vitamin D Receptor (VDR) in mediating the calcemic actions of
CY10012, the analog was daily administered to VDR wt and VDR ko mice. This treatment caused drastic weight loss and death in VDR wt mice but not in VDR ko mice. Conclusion: Analog CY10012 has greater antiproliferative action but also two-fold higher calcemic effects which depended
entirely on VDR-mediated signalling pathways. |
| format | Article |
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disorders. Therefore, analogs of 1,25-(OH) 2 D 3 are designed with a clear dissociation between both effects. Here the biological activity of the trans-decalin CD-ring analog
CY10012 is discussed. Materials and Methods: Proliferation/differentiation/transactivation assays as well as mouse models
were used to determine the activity of CY10012 in vitro and in vivo. Results: CY10012, has ten-fold higher antiproliferative
actions than 1,25(OH) 2 D 3 but is also twice as calcemic. To determine the role of the Vitamin D Receptor (VDR) in mediating the calcemic actions of
CY10012, the analog was daily administered to VDR wt and VDR ko mice. This treatment caused drastic weight loss and death in VDR wt mice but not in VDR ko mice. Conclusion: Analog CY10012 has greater antiproliferative action but also two-fold higher calcemic effects which depended
entirely on VDR-mediated signalling pathways.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>PMID: 19667151</identifier><language>eng</language><publisher>Attiki: International Institute of Anticancer Research</publisher><subject>Animals ; Biological and medical sciences ; Calcitriol - analogs & derivatives ; Calcitriol - pharmacology ; Calcium - metabolism ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cercopithecus aethiops ; COS Cells ; Homeostasis - drug effects ; Humans ; Medical sciences ; Mice ; Mice, Knockout ; Naphthalenes - chemistry ; Receptors, Calcitriol - physiology ; Tumors</subject><ispartof>Anticancer research, 2009-09, Vol.29 (9), p.3579-3584</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>309,310,314,776,780,785,786,23909,23910,25118</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21793552$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19667151$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>EELEN, Guy</creatorcontrib><creatorcontrib>VERLINDEN, Lieve</creatorcontrib><creatorcontrib>LAUREYS, Jos</creatorcontrib><creatorcontrib>MARCELIS, Suzanne</creatorcontrib><creatorcontrib>DE CLERCQ, Pierre</creatorcontrib><creatorcontrib>MATHIEU, Chantal</creatorcontrib><creatorcontrib>BOUILLON, Roger</creatorcontrib><creatorcontrib>VERSTUYF, Annemieke</creatorcontrib><title>Antiproliferative and Calcemic Actions of Trans-Decalin CD-Ring Analogs of 1,25-Dihydroxyvitamin D3</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>Background: 1,25-Dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] has potent antiproliferative actions but calcemic effects obstruct its application in the treatment of hyperproliferative
disorders. Therefore, analogs of 1,25-(OH) 2 D 3 are designed with a clear dissociation between both effects. Here the biological activity of the trans-decalin CD-ring analog
CY10012 is discussed. Materials and Methods: Proliferation/differentiation/transactivation assays as well as mouse models
were used to determine the activity of CY10012 in vitro and in vivo. Results: CY10012, has ten-fold higher antiproliferative
actions than 1,25(OH) 2 D 3 but is also twice as calcemic. To determine the role of the Vitamin D Receptor (VDR) in mediating the calcemic actions of
CY10012, the analog was daily administered to VDR wt and VDR ko mice. This treatment caused drastic weight loss and death in VDR wt mice but not in VDR ko mice. Conclusion: Analog CY10012 has greater antiproliferative action but also two-fold higher calcemic effects which depended
entirely on VDR-mediated signalling pathways.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcitriol - analogs & derivatives</subject><subject>Calcitriol - pharmacology</subject><subject>Calcium - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cercopithecus aethiops</subject><subject>COS Cells</subject><subject>Homeostasis - drug effects</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Naphthalenes - chemistry</subject><subject>Receptors, Calcitriol - physiology</subject><subject>Tumors</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0F1LwzAYBeAgipvTvyC90SsDSfPR5rK0fsFAkHkd0jRdI2k7k266f2_UqVfvzcPhPecIzHEmMMwYQcdgjlKGYIYQm4GzEF4R4lzk5BTMsOA8wwzPgS6GyW786GxrvJrsziRqaJJSOW16q5NCT3YcQjK2ycqrIcDKaOXskJQVfLbDOikG5cb1N8A3KYOV7faNHz_2OzupPsKKnIOTVrlgLg53AV7ublflA1w-3T-WxRJ2OKcTNLVmqKYmIzWjDddC61yTxtCUYUI5ZQ2uNReUsKwhdZpHJnAsRFtidEMFWYDrn9zY521rwiR7G7RxTg1m3AbJM8YpRV_w8gC3dW8aufG2V34vf2eJ4OoAVIh129hc2_Dn0jgyYSz9d51dd-_WGxl65VyMJVL5VEgh47eCfAIivXfc</recordid><startdate>200909</startdate><enddate>200909</enddate><creator>EELEN, Guy</creator><creator>VERLINDEN, Lieve</creator><creator>LAUREYS, Jos</creator><creator>MARCELIS, Suzanne</creator><creator>DE CLERCQ, Pierre</creator><creator>MATHIEU, Chantal</creator><creator>BOUILLON, Roger</creator><creator>VERSTUYF, Annemieke</creator><general>International Institute of Anticancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200909</creationdate><title>Antiproliferative and Calcemic Actions of Trans-Decalin CD-Ring Analogs of 1,25-Dihydroxyvitamin D3</title><author>EELEN, Guy ; VERLINDEN, Lieve ; LAUREYS, Jos ; MARCELIS, Suzanne ; DE CLERCQ, Pierre ; MATHIEU, Chantal ; BOUILLON, Roger ; VERSTUYF, Annemieke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h184t-ebc50b4e73b54d6c9cc8c3de425134645d1bc694357d3b283b5916984f3ecd493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calcitriol - analogs & derivatives</topic><topic>Calcitriol - pharmacology</topic><topic>Calcium - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cercopithecus aethiops</topic><topic>COS Cells</topic><topic>Homeostasis - drug effects</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Naphthalenes - chemistry</topic><topic>Receptors, Calcitriol - physiology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>EELEN, Guy</creatorcontrib><creatorcontrib>VERLINDEN, Lieve</creatorcontrib><creatorcontrib>LAUREYS, Jos</creatorcontrib><creatorcontrib>MARCELIS, Suzanne</creatorcontrib><creatorcontrib>DE CLERCQ, Pierre</creatorcontrib><creatorcontrib>MATHIEU, Chantal</creatorcontrib><creatorcontrib>BOUILLON, Roger</creatorcontrib><creatorcontrib>VERSTUYF, Annemieke</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>EELEN, Guy</au><au>VERLINDEN, Lieve</au><au>LAUREYS, Jos</au><au>MARCELIS, Suzanne</au><au>DE CLERCQ, Pierre</au><au>MATHIEU, Chantal</au><au>BOUILLON, Roger</au><au>VERSTUYF, Annemieke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiproliferative and Calcemic Actions of Trans-Decalin CD-Ring Analogs of 1,25-Dihydroxyvitamin D3</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2009-09</date><risdate>2009</risdate><volume>29</volume><issue>9</issue><spage>3579</spage><epage>3584</epage><pages>3579-3584</pages><issn>0250-7005</issn><eissn>1791-7530</eissn><abstract>Background: 1,25-Dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] has potent antiproliferative actions but calcemic effects obstruct its application in the treatment of hyperproliferative
disorders. Therefore, analogs of 1,25-(OH) 2 D 3 are designed with a clear dissociation between both effects. Here the biological activity of the trans-decalin CD-ring analog
CY10012 is discussed. Materials and Methods: Proliferation/differentiation/transactivation assays as well as mouse models
were used to determine the activity of CY10012 in vitro and in vivo. Results: CY10012, has ten-fold higher antiproliferative
actions than 1,25(OH) 2 D 3 but is also twice as calcemic. To determine the role of the Vitamin D Receptor (VDR) in mediating the calcemic actions of
CY10012, the analog was daily administered to VDR wt and VDR ko mice. This treatment caused drastic weight loss and death in VDR wt mice but not in VDR ko mice. Conclusion: Analog CY10012 has greater antiproliferative action but also two-fold higher calcemic effects which depended
entirely on VDR-mediated signalling pathways.</abstract><cop>Attiki</cop><pub>International Institute of Anticancer Research</pub><pmid>19667151</pmid><tpages>6</tpages></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Biological and medical sciences Calcitriol - analogs & derivatives Calcitriol - pharmacology Calcium - metabolism Cell Line, Tumor Cell Proliferation - drug effects Cercopithecus aethiops COS Cells Homeostasis - drug effects Humans Medical sciences Mice Mice, Knockout Naphthalenes - chemistry Receptors, Calcitriol - physiology Tumors |
| title | Antiproliferative and Calcemic Actions of Trans-Decalin CD-Ring Analogs of 1,25-Dihydroxyvitamin D3 |
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