New study below.
AR-V7 [Androgen Receptor Splice Variant-7] is an Androgen Receptor [AR] mutation that is common in CRPC [castration resistant PCa]. AR-V7 does not need androgen to become active.
"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."
I take 50 mg before bed.
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"It is worth noting that melatonin, which acts by inhibiting both activated AR and NF-κB signaling in prostate cancer cells, has been demonstrated to be a novel prostate growth inhibitor]. Given that constitutively active androgen receptor splice variants, in particular AR-V7, have been shown to confer resistance to abiraterone or enzalutamide, and that activation of NF-κB and reactivation of AR signaling are involved in prostate cancer progression and CRPC development, it would be of interest to investigate any interactions among AR-V7, NF-κB, and melatonin in prostate cancer cells to gain further insights on the therapeutic potential of melatonin in advanced prostate cancer and CRPC management."
-Patrick
ncbi.nlm.nih.gov/pubmed/285...
FULL Text: mdpi.com/1422-0067/18/6/113...
Int J Mol Sci. 2017 May 31;18(6). pii: E1130. doi: 10.3390/ijms18061130.
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.
Liu VWSWS1, Yau WL2, Tam CW3, Yao KM4, Shiu SYWYW5.
Author information
Abstract
A 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.
KEYWORDS:
androgen receptor splice variant-7; castration-resistant prostate cancer; melatonin; nuclear factor-kappa B
PMID: 28561752 DOI: 10.3390/ijms18061130
