Abstract
Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in choriocarcinomas, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. HDAC inhibitors (HDACIs) were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and the expression of genes related to the malignant phenotype in choriocarcinoma cell lines. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating choriocarcinoma, with a special focus on preclinical studies.
Highlights
Gestational choriocarcinoma, a group of rare placenta disorders, have varying potential for invasion, either local, or remote in the form of metastases
histone deacetylase (HDAC) catalyze the removal of acetyl groups on the amino-terminal lysine residues of core nucleosomal histones, and this activity is generally associated with transcriptional repression
HDACs remove the acetyl groups which induce a positive charge on the histones, and this suppresses gene transcription, including tumor suppressor genes silenced in cancer
Summary
Gestational choriocarcinoma, a group of rare placenta disorders, have varying potential for invasion, either local, or remote in the form of metastases. Silent chromatin is composed of nucleosomes in which the histones have low levels of acetylation on the lysine residues of their. Acetylation of histone proteins neutralizes the positive charge on lysine residues and disrupts the nucleosome structure, allowing unfolding of the associated DNA with subsequent access by transcription factors, resulting in changes in gene expression. Acetylation of core nucleosomal histones is regulated by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs catalyze the removal of acetyl groups on the amino-terminal lysine residues of core nucleosomal histones, and this activity is generally associated with transcriptional repression. HDACs remove the acetyl groups which induce a positive charge on the histones, and this suppresses gene transcription, including tumor suppressor genes silenced in cancer. There is no clinical trial for treating choriocarcinoma. We discuss the biologic and therapeutic effects of HDACIs in treating choriocarcinoma, with a special focus on preclinical studies
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