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Article: Signaling mechanisms of melatonin in antiproliferation of hormone-refractory 22Rv1 human prostate cancer cells: Implications for prostate cancer chemoprevention

TitleSignaling mechanisms of melatonin in antiproliferation of hormone-refractory 22Rv1 human prostate cancer cells: Implications for prostate cancer chemoprevention
Authors
KeywordsAndrogen
Chemoprevention
Melatonin
p27Kip1
Prostate-specific antigen
Protein kinase A
Protein kinase C
Issue Date2007
PublisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JPI
Citation
Journal Of Pineal Research, 2007, v. 42 n. 2, p. 191-202 How to Cite?
AbstractThere is an unmet clinical demand for safe and effective pharmaceuticals/nutraceuticals for prostate cancer prevention and hormone-refractory prostate cancer treatment. Previous laboratory and human studies of our laboratory demonstrated an association between the antiproliferative action of melatonin and melatonin MT1 receptor expression in prostate cancer. The aim of this study was to determine, using a pharmacological approach, the signaling mechanisms of melatonin in hormone-refractory 22Rv1 human prostate cancer cell antiproliferation. Both immunoreactive MT1 and MT2 subtypes of G protein-coupled melatonin receptor were expressed in 22Rv1 cells. Melatonin inhibited, concentration dependently, cell proliferation, upregulated p27Kip1 gene transcription and protein expression, and downregulated activated androgen signaling in 22Rv1 cells. While the effects of melatonin were mimicked by 2-iodomelatonin, a high-affinity nonselective MT1 and MT2 receptor agonist, melatonin effects were blocked by luzindole, a nonselective MT1 and MT2 receptor antagonist, but were unaffected by 4-phenyl-2-propionamidotetraline, a selective MT2 receptor antagonist. Importantly, we discovered that the antiproliferative effect of melatonin exerted via MT1 receptor on p27Kip1 gene and protein upregulation is mediated by a novel signaling mechanism involving co-activation of protein kinase C (PKC) and PKA in parallel. Moreover, we also showed that a melatonin/MT1/PKC mechanism is involved in melatonin-induced downregulation of activated androgen signal transduction in 22Rv1 cells. Taken together with the known molecular mechanisms of prostate cancer progression and transition to androgen independence, our data provide strong support for melatonin to be a promising small-molecule useful for prostate cancer primary prevention and secondary prevention of the development and progression of hormone refractoriness. © 2007 The Authors.
Persistent Identifierhttp://hdl.handle.net/10722/68184
ISSN
2015 Impact Factor: 9.314
2015 SCImago Journal Rankings: 2.655
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTam, CWen_HK
dc.contributor.authorMo, CWen_HK
dc.contributor.authorYao, KMen_HK
dc.contributor.authorShiu, SYWen_HK
dc.date.accessioned2010-09-06T06:02:09Z-
dc.date.available2010-09-06T06:02:09Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of Pineal Research, 2007, v. 42 n. 2, p. 191-202en_HK
dc.identifier.issn0742-3098en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68184-
dc.description.abstractThere is an unmet clinical demand for safe and effective pharmaceuticals/nutraceuticals for prostate cancer prevention and hormone-refractory prostate cancer treatment. Previous laboratory and human studies of our laboratory demonstrated an association between the antiproliferative action of melatonin and melatonin MT1 receptor expression in prostate cancer. The aim of this study was to determine, using a pharmacological approach, the signaling mechanisms of melatonin in hormone-refractory 22Rv1 human prostate cancer cell antiproliferation. Both immunoreactive MT1 and MT2 subtypes of G protein-coupled melatonin receptor were expressed in 22Rv1 cells. Melatonin inhibited, concentration dependently, cell proliferation, upregulated p27Kip1 gene transcription and protein expression, and downregulated activated androgen signaling in 22Rv1 cells. While the effects of melatonin were mimicked by 2-iodomelatonin, a high-affinity nonselective MT1 and MT2 receptor agonist, melatonin effects were blocked by luzindole, a nonselective MT1 and MT2 receptor antagonist, but were unaffected by 4-phenyl-2-propionamidotetraline, a selective MT2 receptor antagonist. Importantly, we discovered that the antiproliferative effect of melatonin exerted via MT1 receptor on p27Kip1 gene and protein upregulation is mediated by a novel signaling mechanism involving co-activation of protein kinase C (PKC) and PKA in parallel. Moreover, we also showed that a melatonin/MT1/PKC mechanism is involved in melatonin-induced downregulation of activated androgen signal transduction in 22Rv1 cells. Taken together with the known molecular mechanisms of prostate cancer progression and transition to androgen independence, our data provide strong support for melatonin to be a promising small-molecule useful for prostate cancer primary prevention and secondary prevention of the development and progression of hormone refractoriness. © 2007 The Authors.en_HK
dc.languageengen_HK
dc.publisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JPIen_HK
dc.relation.ispartofJournal of Pineal Researchen_HK
dc.subjectAndrogenen_HK
dc.subjectChemopreventionen_HK
dc.subjectMelatoninen_HK
dc.subjectp27Kip1en_HK
dc.subjectProstate-specific antigenen_HK
dc.subjectProtein kinase Aen_HK
dc.subjectProtein kinase Cen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshCell Proliferationen_HK
dc.subject.meshGrowth Inhibitors - physiologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMelatonin - physiologyen_HK
dc.subject.meshProstatic Neoplasms - metabolism - pathology - prevention & controlen_HK
dc.subject.meshSignal Transduction - physiologyen_HK
dc.titleSignaling mechanisms of melatonin in antiproliferation of hormone-refractory 22Rv1 human prostate cancer cells: Implications for prostate cancer chemopreventionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0742-3098&volume=42&spage=191&epage=202&date=2007&atitle=Signaling+mechanisms+of+melatonin+in+antiproliferation+of+hormone-refractory+22Rv1+human+prostate+cancer+cells:+implications+for+prostate+cancer+chemopreventionen_HK
dc.identifier.emailYao, KM: kmyao@hku.hken_HK
dc.identifier.emailShiu, SYW: sywshiu@hkucc.hku.hken_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.identifier.authorityShiu, SYW=rp00384en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1600-079X.2006.00406.xen_HK
dc.identifier.pmid17286752en_HK
dc.identifier.scopuseid_2-s2.0-33846932844en_HK
dc.identifier.hkuros126141en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33846932844&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume42en_HK
dc.identifier.issue2en_HK
dc.identifier.spage191en_HK
dc.identifier.epage202en_HK
dc.identifier.isiWOS:000244004200013-
dc.publisher.placeDenmarken_HK
dc.identifier.scopusauthoridTam, CW=7201442977en_HK
dc.identifier.scopusauthoridMo, CW=35074658800en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.scopusauthoridShiu, SYW=7005550655en_HK
dc.identifier.citeulike1099410-

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