Related Experiment Video

Updated: Mar 1, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

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Melatonin Inhibits Androgen Receptor Splice Variant-7 (AR-V7)-Induced Nuclear Factor-Kappa B (NF-κB) Activation and

Vincent Wing Sun Liu1, Wing Lung Yau2, Chun Wai Tam3

  • 1School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China. vwsliu@hku.hk.

International Journal of Molecular Sciences
|June 1, 2017
PubMed

Insights

Melatonin inhibits the interaction between androgen receptor variant-7 (AR-V7) and nuclear factor-kappa B (NF-κB) signaling. This disruption delays castration resistance in advanced prostate cancer, offering a potential new therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Advanced prostate cancer often progresses to castration resistance despite initial treatment.
  • Androgen receptor splice variant-7 (AR-V7) and nuclear factor-kappa B (NF-κB) signaling are implicated in castration-resistant prostate cancer (CRPC) pathogenesis.
  • Interleukin-6 (IL-6) is a key mediator in CRPC progression.

Purpose of the Study:

  • To investigate the interaction between AR-V7 and NF-κB/IL-6 signaling in prostate cancer cells.
  • To evaluate the effect of melatonin on AR-V7-induced NF-κB activation and IL-6 expression.
  • To explore the therapeutic potential of melatonin in delaying castration resistance.

Main Methods:

  • Utilized LNCaP and 22Rv1 prostate cancer cell lines.
  • Overexpressed AR-V7 in cell lines.
  • Assessed NF-κB activation and IL-6 gene expression.
  • Treated cells with melatonin and betulinic acid (NF-κB activator).

Main Results:

  • AR-V7 overexpression activated NF-κB and up-regulated IL-6 expression.
  • Melatonin inhibited AR-V7-induced NF-κB activation and IL-6 transcription.
  • Melatonin reduced AR-V7 mRNA expression stimulated by betulinic acid.
  • Demonstrated bi-directional positive interactions between AR-V7 and NF-κB.

Conclusions:

  • Melatonin disrupts the positive feedback loop between AR-V7 and NF-κB signaling.
  • Melatonin inhibits NF-κB activation via the MT₁ receptor pathway.
  • Melatonin holds therapeutic potential for advanced prostate cancer and CRPC management.
  • Combined androgen depletion and melatonin repletion may be a viable clinical strategy.
Keywords:
androgen receptor splice variant-7castration-resistant prostate cancermelatoninnuclear factor-kappa B

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