The Effects of Histone Deacetylase Inhibitor and Calpain Inhibitor Combination Therapies on Ovarian Cancer Cells

Karolina Lapinska1,2, Genevieve Housman3, Shannon Byler4

  • 1Cancer Center, Department of Medicine, Boston University School of Medicine, Boston, MA, U.S.A.

Anticancer Research
|October 30, 2016
PubMed
Abstract

Insights

Combination epigenetic and calpain inhibitor therapy shows promise for ovarian cancer treatment by re-expressing tumor suppressors and inducing cell death. This approach enhances growth inhibition and sensitizes cancer cells, offering a potential alternative to conventional drugs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Ovarian cancer treatment is challenging due to a lack of targeted drugs and platinum drug resistance.
  • Combination therapy with epigenetic drugs presents a promising alternative strategy.

Purpose of the Study:

  • To investigate the synergistic effects of histone deacetylase inhibitors (HDACi) and a calpain inhibitor on ovarian cancer cell lines.
  • To evaluate the impact of combination therapy on tumor suppressor gene re-expression, cell cycle, apoptosis, and autophagy.

Main Methods:

  • Utilized two HDAC inhibitors (sodium butyrate, SAHA) and the calpain inhibitor calpeptin.
  • Tested combination therapies on CAOV-3 and SKOV-3 ovarian cancer cell lines.
  • Assessed gene re-expression, DNA methylation, cell cycle progression, apoptosis, and autophagy.

Main Results:

  • Combination therapy enhanced growth inhibition and re-expressed epigenetically silenced tumor suppressor genes (ARHI, p21, RARβ2).
  • Reduced methylation of CpG residues in the ARHI gene was observed.
  • Inhibited cell-cycle progression and induced apoptosis and autophagy.
  • Differential effects on ERK and Akt phosphorylation were noted.

Conclusions:

  • Re-expression of tumor suppressors sensitizes ovarian cancer cells to therapy.
  • Combination treatment with HDAC inhibitors and calpeptin promotes cancer cell death through apoptosis and autophagy.

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