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Panobinostat reverses HepaCAM gene expression and suppresses proliferation by increasing histone acetylation in

E Chen1, NanJing Liu2, Yan Zhao2

  • 1The Key Laboratory of Diagnostics Medicine, Ministry of Education, Chongqing Medical University, Chongqing 400016, People's Republic of China; Center for Clinical Molecular Medicine, Children's Hospital, Chongqing Medical University, Chongqing 400015, People's Republic of China.

Gene
|September 30, 2021
PubMed

Insights

Panobinostat, a histone deacetylase inhibitor, re-expresses the tumor suppressor hepaCAM in prostate cancer cells. Combining panobinostat with Ad-hepaCAM synergistically inhibits cancer growth and overcomes resistance to androgen deprivation therapy.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Prostate cancer (PCa) frequently exhibits increased histone deacetylases (HDACs) and decreased expression of the tumor suppressor hepatocyte cell adhesion molecule (hepaCAM).
  • The mechanisms underlying hepaCAM downregulation in PCa remain unclear, though histone acetylation is implicated in tumor suppressor gene expression.

Purpose of the Study:

  • To investigate the effect of panobinostat, a broad-spectrum HDAC inhibitor, on PCa cell growth and hepaCAM re-expression.
  • To explore the potential of combining panobinostat with Ad-hepaCAM as a therapeutic strategy for PCa.

Main Methods:

  • Treatment of PCa cell lines (LNCaP and DU145) with panobinostat.
  • Analysis of histone acetylation (Ac-H3K9) and HDAC expression (HDAC1, HDAC3, HDAC4) via Western blot.
  • Assessment of hepaCAM and androgen receptor (AR) expression in PCa tissues.
  • Combination therapy studies with panobinostat and Ad-hepaCAM, evaluating cell proliferation markers (CCND1, PCNA).

Main Results:

  • Panobinostat treatment increased intranuclear histone H3 acetylation (Ac-H3K9) and decreased HDAC1, HDAC3, and HDAC4 expression in PCa cells.
  • Re-expression of hepaCAM and AR was observed, correlating with histone acetylation levels in PCa tissues.
  • Panobinostat demonstrated efficacy in overcoming resistance to androgen deprivation therapy (ADT).
  • Combined panobinostat and Ad-hepaCAM therapy showed synergistic antitumor activity, significantly reducing CCND1 and PCNA expression.

Conclusions:

  • Panobinostat enhances histone H3 acetylation and reverses hepaCAM expression in PCa cells by inhibiting HDAC activity.
  • Combination therapy with Ad-hepaCAM and panobinostat offers a synergistic approach to inhibit PCa cell growth, potentially through downregulating CCND1 and PCNA.
  • This therapeutic strategy warrants further investigation in clinical trials for prostate cancer treatment.
Keywords:
HepaCAMHistone deacetylasePanobinostatProstate Cancer

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