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Article: Melatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC) Therapy

TitleMelatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC) Therapy
Authors
KeywordsAndrogen receptor splice variant-7
Castration-resistant prostate cancer
Melatonin
Nuclear factor-kappa B
Issue Date2017
PublisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms
Citation
International Journal of Molecular Sciences, 2017, v. 18 n. 6, p. 1130 How to Cite?
AbstractA major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7), nuclear factor-kappa B (NF-κB) was activated and could result in up-regulated interleukin (IL)-6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC) pathogenesis. Importantly, both AR-V7-induced NF-κB activation and IL-6 gene transcription in LNCaP and 22Rv1 cells could be inhibited by melatonin. Furthermore, stimulation of AR-V7 mRNA expression in LNCaP cells by betulinic acid, a pharmacological NF-κB activator, was reduced by melatonin treatment. Our data support the presence of bi-directional positive interactions between AR-V7 expression and NF-κB activation in CRPC pathogenesis. Of note, melatonin, by inhibiting NF-κB activation via the previously-reported MT₁ receptor-mediated antiproliferative pathway, can disrupt these bi-directional positive interactions between AR-V7 and NF-κB and thereby delay the development of castration resistance in advanced prostate cancer. Apparently, this therapeutic potential of melatonin in advanced prostate cancer/CRPC management is worth translation in the clinic via combined androgen depletion and melatonin repletion.
Persistent Identifierhttp://hdl.handle.net/10722/246881
ISSN
2020 Impact Factor: 5.923
2020 SCImago Journal Rankings: 1.455
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, VWS-
dc.contributor.authorYao, WL-
dc.contributor.authorTam, CW-
dc.contributor.authorYao, KM-
dc.contributor.authorShiu, SYW-
dc.date.accessioned2017-10-18T08:18:48Z-
dc.date.available2017-10-18T08:18:48Z-
dc.date.issued2017-
dc.identifier.citationInternational Journal of Molecular Sciences, 2017, v. 18 n. 6, p. 1130-
dc.identifier.issn1422-0067-
dc.identifier.urihttp://hdl.handle.net/10722/246881-
dc.description.abstractA major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7), nuclear factor-kappa B (NF-κB) was activated and could result in up-regulated interleukin (IL)-6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC) pathogenesis. Importantly, both AR-V7-induced NF-κB activation and IL-6 gene transcription in LNCaP and 22Rv1 cells could be inhibited by melatonin. Furthermore, stimulation of AR-V7 mRNA expression in LNCaP cells by betulinic acid, a pharmacological NF-κB activator, was reduced by melatonin treatment. Our data support the presence of bi-directional positive interactions between AR-V7 expression and NF-κB activation in CRPC pathogenesis. Of note, melatonin, by inhibiting NF-κB activation via the previously-reported MT₁ receptor-mediated antiproliferative pathway, can disrupt these bi-directional positive interactions between AR-V7 and NF-κB and thereby delay the development of castration resistance in advanced prostate cancer. Apparently, this therapeutic potential of melatonin in advanced prostate cancer/CRPC management is worth translation in the clinic via combined androgen depletion and melatonin repletion.-
dc.languageeng-
dc.publisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms-
dc.relation.ispartofInternational Journal of Molecular Sciences-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAndrogen receptor splice variant-7-
dc.subjectCastration-resistant prostate cancer-
dc.subjectMelatonin-
dc.subjectNuclear factor-kappa B-
dc.titleMelatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and NF-κB Activator-Induced AR-V7 Expression in Prostate Cancer Cells: Potential Implications for the Use of Melatonin in Castration-Resistant Prostate Cancer (CRPC) Therapy-
dc.typeArticle-
dc.identifier.emailLiu, VWS: vwsliu@hku.hk-
dc.identifier.emailYao, KM: kmyao@hku.hk-
dc.identifier.emailShiu, SYW: sywshiu@hku.hk-
dc.identifier.authorityLiu, VWS=rp00341-
dc.identifier.authorityYao, KM=rp00344-
dc.identifier.authorityShiu, SYW=rp00384-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/ijms18061130-
dc.identifier.scopuseid_2-s2.0-85020234823-
dc.identifier.hkuros279861-
dc.identifier.volume18-
dc.identifier.issue6-
dc.identifier.spage1130-
dc.identifier.epage1130-
dc.identifier.isiWOS:000404581500030-
dc.publisher.placeSwitzerland-
dc.identifier.issnl1422-0067-

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