Drug-induced inactivation or gene silencing of class I histone deacetylases suppresses ovarian cancer cell growth: Implications for therapy

Dineo Khabele, Deok Soo Son, Angelika K. Parl, Gary L. Goldberg, Leonard H. Augenlicht, John M. Mariadason, Valerie Montgomery Rice

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

There is an urgent need to develop new strategies to treat ovarian cancer, the most deadly gynecologic malignancy. Histone deacetylase (HDAC) inhibitors are emerging as novel therapeutic drugs in the treatment of a variety of cancers, including those resistant to standard chemotherapy. Since there are multiple HDAC isoforms, determining the precise role of individual HDAC isoenzymes in the growth and progression of ovarian cancer has the potential to influence the use of selective HDAC inhibitors as strategic therapeutic agents that elicit fewer undesirable side effects. Unfortunately, there is limited information about the expression of HDAC isoforms in human ovarian tissues. This report provides evidence for the first time that Class I HDACs are expressed at significantly higher levels in ovarian cancers in comparison to normal ovarian tissues, with no significant difference in Class II HDAC expression between the two groups. Furthermore, ovarian cancer cells are far more sensitive than normal ovarian cells to the potent HDAC inhibitor romidepsin (FK228), a drug that displays greater inhibitory selectivity for Class I HDACs over Class II isoforms. Using small interfering RNA (siRNA) methodology, we demonstrate that knocking down the gene expression of HDAC3 and other members of the Class I HDAC family suppresses ovarian cancer cell growth. Taken together, the present studies offer several novel findings that have direct relevance for the strategic use of inhibitors that target Class I HDACs, particularly HDAC3, in the treatment of ovarian cancer.

Original languageEnglish (US)
Pages (from-to)795-801
Number of pages7
JournalCancer Biology and Therapy
Volume6
Issue number5
StatePublished - May 2007

Fingerprint

Histone Deacetylases
Gene Silencing
Ovarian Neoplasms
Histone Deacetylase Inhibitors
Growth
Pharmaceutical Preparations
Protein Isoforms
Therapeutics
Small Interfering RNA
Isoenzymes
Neoplasms
Gene Expression
Drug Therapy

Keywords

  • Cancer biology
  • FK228
  • Histone deacetylases
  • Molecular therapy
  • Ovarian cancer
  • siRNA
  • Surgical oncology

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Drug-induced inactivation or gene silencing of class I histone deacetylases suppresses ovarian cancer cell growth : Implications for therapy. / Khabele, Dineo; Son, Deok Soo; Parl, Angelika K.; Goldberg, Gary L.; Augenlicht, Leonard H.; Mariadason, John M.; Rice, Valerie Montgomery.

In: Cancer Biology and Therapy, Vol. 6, No. 5, 05.2007, p. 795-801.

Research output: Contribution to journalArticle

Khabele, Dineo ; Son, Deok Soo ; Parl, Angelika K. ; Goldberg, Gary L. ; Augenlicht, Leonard H. ; Mariadason, John M. ; Rice, Valerie Montgomery. / Drug-induced inactivation or gene silencing of class I histone deacetylases suppresses ovarian cancer cell growth : Implications for therapy. In: Cancer Biology and Therapy. 2007 ; Vol. 6, No. 5. pp. 795-801.
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