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Vorinostat and bortezomib synergistically cause ubiquitinated protein accumulation in prostate cancer cells

Akinori Sato1, Takako Asano, Keiichi Ito

  • 1Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan. zenpaku@ndmc.ac.jp

The Journal of Urology
|October 24, 2012
PubMed
Abstract

Insights

Combining vorinostat and bortezomib synergistically inhibits prostate cancer growth by increasing protein ubiquitination and apoptosis. This combination therapy shows promise for advanced prostate cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Protein ubiquitination is an emerging strategy for cancer treatment.
  • Histone deacetylase inhibitors (e.g., vorinostat) and proteasome inhibitors (e.g., bortezomib) are classes of drugs with anti-cancer potential.

Purpose of the Study:

  • To investigate the synergistic effect of vorinostat and bortezomib on prostate cancer cells.
  • To determine if this combination induces accumulation of ubiquitinated proteins in prostate cancer.

Main Methods:

  • Prostate cancer cell lines (LNCaP, PC-3, DU 145) were treated with vorinostat and/or bortezomib.
  • Assessed cell viability, apoptosis, and tumor growth in a murine xenograft model.
  • Examined androgen receptor expression's influence on bortezomib efficacy and evaluated protein expression changes.

Main Results:

  • Vorinostat and bortezomib synergistically induced apoptosis and inhibited prostate cancer cell and tumor growth.
  • The combination led to the accumulation of ubiquitinated proteins and histone acetylation, decreasing cyclin D1/CDK4 and increasing p21.
  • Androgen receptor expression negatively impacted bortezomib efficacy; its silencing enhanced activity.

Conclusions:

  • Vorinostat and bortezomib demonstrate synergistic inhibition of prostate cancer cell growth via accumulation of ubiquitinated proteins.
  • This combination therapy provides a potential treatment strategy for advanced prostate cancer.

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