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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Raddeanin A down-regulates androgen receptor and its splice variants in prostate cancer

Hongyan Xia1, Cheng Hu1, Shanshan Bai1,2

  • 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.

Journal of Cellular and Molecular Medicine
|March 25, 2019
PubMed

Insights

Raddeanin A (RA) targets both full-length and splice variants of the androgen receptor (AR), crucial drivers of prostate cancer mortality. This natural compound offers a new therapeutic strategy for advanced prostate cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Castration-resistant prostate cancer (CRPC) progression is a significant cause of cancer mortality.
  • Increased expression and activity of androgen receptor (AR) variants drive CRPC.
  • A need exists for agents targeting both full-length and splice variants of AR.

Purpose of the Study:

  • To investigate the potential of raddeanin A (RA) as a therapeutic agent against CRPC.
  • To determine RA's mechanism of action on AR transcriptional activity.
  • To evaluate RA's efficacy in combination with docetaxel for prostate cancer treatment.

Main Methods:

  • Assessed the effect of RA on the transcriptional activity of full-length and splice variants of AR.
  • Investigated RA's impact on AR gene expression and protein degradation pathways.
  • Evaluated the combined efficacy of RA and docetaxel in preclinical models.

Main Results:

  • Raddeanin A suppressed the transcriptional activities of both full-length and splice variants of AR.
  • RA decreased AR expression by inducing proteasome-mediated degradation and inhibiting AR gene transcription.
  • RA enhanced the growth inhibitory effects of docetaxel, a standard chemotherapy for prostate cancer.

Conclusions:

  • Raddeanin A is identified as a novel agent targeting both full-length and splice variants of AR.
  • RA demonstrates a dual mechanism of action involving AR degradation and transcriptional inhibition.
  • RA shows potential for combination therapy to improve treatment outcomes in advanced prostate cancer.
Keywords:
androgen receptorcastration-resistant prostate cancerraddeanin Asplice variant

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