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


Journal Article

OBJECTIVE: To characterize the molecular pathways involved in apoptosis following administration of histone deacetylase inhibitors to Type I and II endometrial cancer cells. METHODS: Ark2, Ishikawa, and AN3 cell lines representing both Type I and II endometrial cancers were treated with various concentrations of oxamflatin and HDAC inhibitor-1. Cell apoptosis was determined by flow cytometry, nuclear staining, Western blotting, and mitochondrial membrane potential assays. RESULTS: Compared to controls, there was a 95% reduction in the growth of Ark2 cells following administration of histone deacetylase inhibitors and this response was dose-dependent. These agents also caused profound morphologic changes and loss of mitochondrial membrane potentials consistent with the induction of apoptosis. Cleavage of PARP, caspase-9, and caspase-8 was detected, confirming the activation of apoptotic cascades in endometrial carcinoma cells. This effect was present in both serous and endometrioid cell types. CONCLUSION: Our results suggest that oxamflatin and HDAC inhibitor-1 have potent cytotoxicity in endometrial cancer cells by inducing cell apoptosis. Histone deacetylase inhibitors are promising agents for the treatment of both Type I and II endometrial carcinoma.

Full Text

Cited Authors

  • Jiang, S; Dowdy, SC; Meng, XW; Wang, Z; Jones, MB; Podratz, KC; Jiang, S-W

Published Date

  • May 2007

Published In

Volume / Issue

  • 105 / 2

Start / End Page

  • 493 - 500

PubMed ID

  • 17303224

Pubmed Central ID

  • 17303224

International Standard Serial Number (ISSN)

  • 0090-8258

Digital Object Identifier (DOI)

  • 10.1016/j.ygyno.2007.01.012


  • eng

Conference Location

  • United States