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Combination therapy of antiandrogen and XIAP inhibitor for treating advanced prostate cancer

Michael Danquah1, Charles B Duke, Renukadevi Patil

  • 1University of Tennessee Health Science Center, Department of Pharmaceutical Sciences, 19 South Manassas, CRB RM 226, Memphis, 38103-3308, Tennessee, USA.

Pharmaceutical Research
|March 28, 2012
PubMed
Abstract

Insights

A novel combination therapy using antiandrogen (CBDIV17) and XIAP inhibitor (embelin) shows promise for advanced prostate cancer. This treatment effectively reduced tumor growth by inhibiting androgen receptor (AR) and promoting apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Androgen receptor (AR) and X-linked inhibitor of apoptosis protein (XIAP) overexpression promote tumor growth in advanced prostate cancer.
  • Targeting AR and XIAP offers a potential therapeutic strategy.

Purpose of the Study:

  • To evaluate the efficacy of a novel combination therapy involving a new antiandrogen (CBDIV17) and an XIAP inhibitor (embelin) for advanced prostate cancer.
  • To assess the effects of this combination on cancer cell proliferation, apoptosis, and gene expression.

Main Methods:

  • CBDIV17 and embelin were synthesized and tested for their effects on prostate cancer cells (LNCaP, C4-2).
  • Assays included cell proliferation, apoptosis, cell cycle analysis, and AR/XIAP gene silencing.
  • Drug delivery utilized micelles formed with a PEG-b-p(CB-co-LA) copolymer for hydrophobic drugs.
  • In vivo studies assessed tumor growth inhibition.

Main Results:

  • CBDIV17 demonstrated superior potency to bicalutamide in inhibiting proliferation and inducing apoptosis in prostate cancer cells.
  • The combination of CBDIV17 and embelin exhibited supra-additive antiproliferative and apoptotic effects.
  • Embelin downregulated AR expression and reduced androgen-mediated AR phosphorylation.
  • Combination therapy significantly inhibited prostate tumor growth in vivo compared to monotherapy or control.

Conclusions:

  • The combination of CBDIV17 and embelin is a promising therapeutic approach for advanced prostate cancer.
  • This strategy effectively targets key pathways involved in prostate cancer progression.

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