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Histone deacetylase inhibitor therapy in epithelial ovarian cancer.

Takai N, Narahara H - J Oncol (2009)

Bottom Line: Since epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in ovarian cancers, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach.In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs) in treating ovarian cancer.Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21(WAF1) gene in human ovarian carcinoma cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita 879-5593, Japan.

ABSTRACT
Since epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in ovarian cancers, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs) in treating ovarian cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in a variety of ovarian cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21(WAF1) gene in human ovarian carcinoma cells. In xenograft models, some of HDACIs have demonstrated antitumor activity with only few side effects. Some clinical trials demonstrate that HDACI drugs provide an important class of new mechanism-based therapeutics for ovarian cancer. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating ovarian cancer, especially focusing on preclinical studies and clinical trials.

No MeSH data available.


Related in: MedlinePlus

The mechanism of action of HDACIs against ovarian cancer [9].
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig1: The mechanism of action of HDACIs against ovarian cancer [9].

Mentions: HDACIs markedly upregulated the level of p21WAF1 and p27KIP1 proteins, which were expressed at negligible levels in the untreated ovarian cancer cell lines. Conversely, HDACIs decreased the levels of cyclin D1 and cyclin D2. HDACIs decreased bcl-2 levels. E-cadherin binds to β-catenin and can act as a tumor suppressor gene; its promoter has CpG islands which are frequently methylated in selected cancers. Although some investigators believed that the expression of E-cadherin can promote carcinogenesis from normal ovarian surface epithelial cells unlike the other carcinomas [10], HDACIs markedly increased the expression level of E-cadherin in endometrial and ovarian cancer cells and exhibit antiproliferative activity in these cells [11] (Figure 1).


Histone deacetylase inhibitor therapy in epithelial ovarian cancer.

Takai N, Narahara H - J Oncol (2009)

The mechanism of action of HDACIs against ovarian cancer [9].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2801002&req=5

fig1: The mechanism of action of HDACIs against ovarian cancer [9].
Mentions: HDACIs markedly upregulated the level of p21WAF1 and p27KIP1 proteins, which were expressed at negligible levels in the untreated ovarian cancer cell lines. Conversely, HDACIs decreased the levels of cyclin D1 and cyclin D2. HDACIs decreased bcl-2 levels. E-cadherin binds to β-catenin and can act as a tumor suppressor gene; its promoter has CpG islands which are frequently methylated in selected cancers. Although some investigators believed that the expression of E-cadherin can promote carcinogenesis from normal ovarian surface epithelial cells unlike the other carcinomas [10], HDACIs markedly increased the expression level of E-cadherin in endometrial and ovarian cancer cells and exhibit antiproliferative activity in these cells [11] (Figure 1).

Bottom Line: Since epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in ovarian cancers, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach.In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs) in treating ovarian cancer.Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21(WAF1) gene in human ovarian carcinoma cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Oita 879-5593, Japan.

ABSTRACT
Since epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in ovarian cancers, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. In this review, we discuss the biologic and therapeutic effects of HDAC inhibitors (HDACIs) in treating ovarian cancer. HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and expression of genes related to the malignant phenotype in a variety of ovarian cancer cell lines. Furthermore, HDACIs were able to induce the accumulation of acetylated histones in the chromatin of the p21(WAF1) gene in human ovarian carcinoma cells. In xenograft models, some of HDACIs have demonstrated antitumor activity with only few side effects. Some clinical trials demonstrate that HDACI drugs provide an important class of new mechanism-based therapeutics for ovarian cancer. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating ovarian cancer, especially focusing on preclinical studies and clinical trials.

No MeSH data available.


Related in: MedlinePlus