Inhibition of androstenediol-dependent LNCaP tumour growth by 17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235)
Androst-5-ene-3 β , 17 β -diol (AED) is an adrenal hormone that has been reported to sustain prostate cancer growth after androgen deprivation therapy (ADT). LNCaP cells express a mutated androgen receptor that confers the ability to respond not only to androgen but also to oestrogen and adrenal hor...
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| Veröffentlicht in: | British journal of cancer 2009-04, Vol.100 (7), p.1068-1072 |
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| creator | Trauger, R Corey, E Bell, D White, S Garsd, A Stickney, D Reading, C Frincke, J |
| description | Androst-5-ene-3
β
, 17
β
-diol (AED) is an adrenal hormone that has been reported to sustain prostate cancer growth after androgen deprivation therapy (ADT). LNCaP cells express a mutated androgen receptor that confers the ability to respond not only to androgen but also to oestrogen and adrenal hormones such as AED, and thus provide a cell line useful for identifying compounds capable of inhibiting AED-stimulated cell growth. We sought to determine whether structurally related steroids could inhibit AED-stimulated LNCaP cell growth
in vitro
and tumour growth
in vivo
. We report here the identification of a novel androstane steroid, HE3235 (17
α
-ethynyl-5
α
-androstan-3
α
, 17
β
-diol), with significant inhibitory activity for AED-stimulated LNCaP proliferation. This inhibitory activity is accompanied by an increase in the number of apoptotic cells. Animal studies have confirmed the cytoreductive activity of HE3235 on LNCaP tumours. The results suggest that this compound may be of clinical use in castration-resistant prostate cancer. |
| doi_str_mv | 10.1038/sj.bjc.6604987 |
| format | Article |
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β
, 17
β
-diol (AED) is an adrenal hormone that has been reported to sustain prostate cancer growth after androgen deprivation therapy (ADT). LNCaP cells express a mutated androgen receptor that confers the ability to respond not only to androgen but also to oestrogen and adrenal hormones such as AED, and thus provide a cell line useful for identifying compounds capable of inhibiting AED-stimulated cell growth. We sought to determine whether structurally related steroids could inhibit AED-stimulated LNCaP cell growth
in vitro
and tumour growth
in vivo
. We report here the identification of a novel androstane steroid, HE3235 (17
α
-ethynyl-5
α
-androstan-3
α
, 17
β
-diol), with significant inhibitory activity for AED-stimulated LNCaP proliferation. This inhibitory activity is accompanied by an increase in the number of apoptotic cells. Animal studies have confirmed the cytoreductive activity of HE3235 on LNCaP tumours. The results suggest that this compound may be of clinical use in castration-resistant prostate cancer.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/sj.bjc.6604987</identifier><identifier>PMID: 19337256</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Drug Resistance ; Epidemiology ; Medical sciences ; Molecular Medicine ; Nephrology. Urinary tract diseases ; Oncology ; Translational Therapeutics ; Tumors ; Tumors of the urinary system ; Urinary tract. Prostate gland</subject><ispartof>British journal of cancer, 2009-04, Vol.100 (7), p.1068-1072</ispartof><rights>The Author(s) 2009</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © 2009 Cancer Research UK 2009 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3197-a646071de7dfcda84dd7976d19896aa8a0867c1167521c27ca5e31c903deb5073</citedby><cites>FETCH-LOGICAL-c3197-a646071de7dfcda84dd7976d19896aa8a0867c1167521c27ca5e31c903deb5073</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669987/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669987/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21938136$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Trauger, R</creatorcontrib><creatorcontrib>Corey, E</creatorcontrib><creatorcontrib>Bell, D</creatorcontrib><creatorcontrib>White, S</creatorcontrib><creatorcontrib>Garsd, A</creatorcontrib><creatorcontrib>Stickney, D</creatorcontrib><creatorcontrib>Reading, C</creatorcontrib><creatorcontrib>Frincke, J</creatorcontrib><title>Inhibition of androstenediol-dependent LNCaP tumour growth by 17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235)</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><description>Androst-5-ene-3
β
, 17
β
-diol (AED) is an adrenal hormone that has been reported to sustain prostate cancer growth after androgen deprivation therapy (ADT). LNCaP cells express a mutated androgen receptor that confers the ability to respond not only to androgen but also to oestrogen and adrenal hormones such as AED, and thus provide a cell line useful for identifying compounds capable of inhibiting AED-stimulated cell growth. We sought to determine whether structurally related steroids could inhibit AED-stimulated LNCaP cell growth
in vitro
and tumour growth
in vivo
. We report here the identification of a novel androstane steroid, HE3235 (17
α
-ethynyl-5
α
-androstan-3
α
, 17
β
-diol), with significant inhibitory activity for AED-stimulated LNCaP proliferation. This inhibitory activity is accompanied by an increase in the number of apoptotic cells. Animal studies have confirmed the cytoreductive activity of HE3235 on LNCaP tumours. The results suggest that this compound may be of clinical use in castration-resistant prostate cancer.</description><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Medical sciences</subject><subject>Molecular Medicine</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Oncology</subject><subject>Translational Therapeutics</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary tract. Prostate gland</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><recordid>eNp1kMtKAzEUhoMoWqtb17MRFEzNpZPLRpDipVDUha5DJsm0M0wzNZkqfaz6ID6TKS2CC1dJOP__hfMBcIbRACMqrmM9KGozYAwNpeB7oIdzSiAWhO-DHkKIQyQJOgLHMdbpKZHgh-AIS0o5yVkPvI_9rCqqrmp91paZ9ja0sXPe2aptoHUL563zXTZ5GumXrFvO22XIpqH97GZZscow_15D181WftXAPN13AO0dpN_rq03gC25Y2cXjHSU0vzwBB6VuojvdnX3wdn_3OnqEk-eH8eh2Ag3FkkPNhgxxbB23pbFaDK3lkjOLpZBMa6GRYNxgzHhOsCHc6NxRbCSi1hU54rQPbrbcxbKYO2vSFkE3ahGquQ4r1epK_Z34aqam7YcijMnkMgEGW4BJG8Xgyt8uRmojX8VaJflqJz8Vznc_6mh0UwbtTRV_WyRZF5iylLve5mIa-akLqk5WfZLxH_kHz2CW4A</recordid><startdate>20090407</startdate><enddate>20090407</enddate><creator>Trauger, R</creator><creator>Corey, E</creator><creator>Bell, D</creator><creator>White, S</creator><creator>Garsd, A</creator><creator>Stickney, D</creator><creator>Reading, C</creator><creator>Frincke, J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20090407</creationdate><title>Inhibition of androstenediol-dependent LNCaP tumour growth by 17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235)</title><author>Trauger, R ; Corey, E ; Bell, D ; White, S ; Garsd, A ; Stickney, D ; Reading, C ; Frincke, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3197-a646071de7dfcda84dd7976d19896aa8a0867c1167521c27ca5e31c903deb5073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Medical sciences</topic><topic>Molecular Medicine</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Oncology</topic><topic>Translational Therapeutics</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Urinary tract. Prostate gland</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Trauger, R</creatorcontrib><creatorcontrib>Corey, E</creatorcontrib><creatorcontrib>Bell, D</creatorcontrib><creatorcontrib>White, S</creatorcontrib><creatorcontrib>Garsd, A</creatorcontrib><creatorcontrib>Stickney, D</creatorcontrib><creatorcontrib>Reading, C</creatorcontrib><creatorcontrib>Frincke, J</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Pascal-Francis</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Trauger, R</au><au>Corey, E</au><au>Bell, D</au><au>White, S</au><au>Garsd, A</au><au>Stickney, D</au><au>Reading, C</au><au>Frincke, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of androstenediol-dependent LNCaP tumour growth by 17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235)</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><date>2009-04-07</date><risdate>2009</risdate><volume>100</volume><issue>7</issue><spage>1068</spage><epage>1072</epage><pages>1068-1072</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Androst-5-ene-3
β
, 17
β
-diol (AED) is an adrenal hormone that has been reported to sustain prostate cancer growth after androgen deprivation therapy (ADT). LNCaP cells express a mutated androgen receptor that confers the ability to respond not only to androgen but also to oestrogen and adrenal hormones such as AED, and thus provide a cell line useful for identifying compounds capable of inhibiting AED-stimulated cell growth. We sought to determine whether structurally related steroids could inhibit AED-stimulated LNCaP cell growth
in vitro
and tumour growth
in vivo
. We report here the identification of a novel androstane steroid, HE3235 (17
α
-ethynyl-5
α
-androstan-3
α
, 17
β
-diol), with significant inhibitory activity for AED-stimulated LNCaP proliferation. This inhibitory activity is accompanied by an increase in the number of apoptotic cells. Animal studies have confirmed the cytoreductive activity of HE3235 on LNCaP tumours. The results suggest that this compound may be of clinical use in castration-resistant prostate cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19337256</pmid><doi>10.1038/sj.bjc.6604987</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | SpringerLink Journals; Nature Journals Online; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Drug Resistance Epidemiology Medical sciences Molecular Medicine Nephrology. Urinary tract diseases Oncology Translational Therapeutics Tumors Tumors of the urinary system Urinary tract. Prostate gland |
| title | Inhibition of androstenediol-dependent LNCaP tumour growth by 17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235) |
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