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Gynecol Oncol. 2007 May;105(2):493-500. Epub 2007 Feb 15.

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

Author information

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

Abstract

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.

PMID:
17303224
PMCID:
PMC3273418
DOI:
10.1016/j.ygyno.2007.01.012
[Indexed for MEDLINE]
Free PMC Article

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