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Histone deacetylase inhibitors induce apoptosis in both Type I and Type II endometrial cancer cells

Shujuan Jiang1, Sean C Dowdy, Xue W Meng

  • 1Shandong Provincial Hospital, Jinan, P.R. China.

Gynecologic Oncology
|February 17, 2007
PubMed
Abstract

Insights

Histone deacetylase inhibitors like oxamflatin show potent anti-cancer effects in endometrial cancer cells. These drugs induce apoptosis, significantly reducing tumor cell growth in both Type I and II endometrial cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Endometrial cancer comprises Type I (estrogen-dependent) and Type II (estrogen-independent) subtypes.
  • Histone deacetylase inhibitors (HDACi) are an emerging class of anti-cancer agents.

Purpose of the Study:

  • To investigate the molecular mechanisms of apoptosis induced by HDAC inhibitors in Type I and II endometrial cancer cells.
  • To evaluate the efficacy of oxamflatin and a novel HDAC inhibitor in preclinical models of endometrial cancer.

Main Methods:

  • Treatment of Ark2, Ishikawa, and AN3 endometrial cancer cell lines with oxamflatin and HDAC inhibitor-1.
  • Assessment of apoptosis via flow cytometry, nuclear staining, Western blotting, and mitochondrial membrane potential assays.

Main Results:

  • A dose-dependent 95% reduction in Ark2 cell growth was observed with HDAC inhibitor administration.
  • HDAC inhibitors induced significant morphologic changes and loss of mitochondrial membrane potential, indicative of apoptosis.
  • Cleavage of PARP, caspase-9, and caspase-8 confirmed activation of apoptotic pathways in both endometrioid and serous endometrial carcinoma cells.

Conclusions:

  • Oxamflatin and HDAC inhibitor-1 exhibit potent cytotoxicity against endometrial cancer cells through apoptosis induction.
  • HDAC inhibitors represent promising therapeutic candidates for both Type I and Type II endometrial carcinoma.

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