Histone deacetylase inhibitors active against ovarian cancer cells

Histone deacetylase inhibitors (HDACIs), including valproic acid and suberoyl anilide bishydroxamine (SAHA), are effective in inhibiting proliferation and inducing apoptosis in human ovarian cancer cells, researchers report.

“SAHA inhibits the growth of ovarian cancer cells by a mechanism different than chemotherapy and therefore holds the promise to retard the growth of ovarian cancer and other cancers without the same toxicities as chemotherapy,” senior investigator Dr. H. Philip Koeffler told Reuters Health.Dr. Koeffler of the University of California, Los Angeles and colleagues found that nine ovarian cancer cell lines that expressed a mutated nonfunctional form of the p53 protein were sensitive to the growth inhibitory effects of the HDACIs.HDACIs induced apoptosis in concert with alterations in genes, including activation of caspase-9 and caspase-3, related to apoptosis, cell growth, and malignant phenotype, the researchers report in the December 15th issue of Cancer.In immunodeficient mice, valproic acid significantly inhibited human ovarian tumor growth without toxic side effects.Nevertheless, Dr. Koeffler concluded there is a “long road” of trials ahead, “and the true efficacy of this approach to therapy will only become clear over time.”(Source: Cancer 2004;101:2760-2770: Reuters Health: Oncolink: January 2005.)