Abstract
Background:
The effect of histone deacetylase inhibitors (HDACIs) and DNA methyltransferase inhibitors (DNMTIs) on proliferation of endometrial cancer (EC) cells in vitro and in vivo was investigated.
Methods:
Changes in methylation of the CDH1 promoter in HDACI- and DNMTI-treated HEC-1-B and RL-952 EC cells were detected. Nude mice with xenografted implants of human EC HEC-1-B cells were treated with valproic acid (VPA) and decitabine (DAC) and evaluated for tumor growth, CDH1 and Bcl-2 mRNA levels.
Results:
DAC, VPA and suberoylanilide hydroxamic acid (SAHA) inhibited proliferation, induced cell cycle arrest and enhanced the apoptotic index in both cell lines, DAC, VPA and SAHA upregulated E-cadherin mRNA and protein levels and downregulated Bcl-2 mRNA levels in vitro. DAC and VPA inhibited tumor growth, upregulated CDH1 mRNA and downregulated Bcl-2 mRNA levels in vivo.
Conclusions:
A combination of HDACIs and DNMTIs suppresses the growth of EC, which is likely mediated by upregulation of E-cadherin and downregulation of Bcl-2.
Copyright © 2012 S. Karger AG, Basel.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antineoplastic Agents / pharmacology
-
Antineoplastic Agents / therapeutic use
-
Apoptosis / drug effects
-
Azacitidine / analogs & derivatives
-
Azacitidine / pharmacology
-
Azacitidine / therapeutic use
-
Cadherins / genetics
-
Cadherins / metabolism*
-
Carcinoma / drug therapy*
-
Cell Cycle Checkpoints / drug effects
-
Cell Line, Tumor
-
DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors*
-
DNA (Cytosine-5-)-Methyltransferases / metabolism
-
DNA Methylation
-
Decitabine
-
Endometrial Neoplasms / drug therapy*
-
Enzyme Inhibitors / pharmacology*
-
Enzyme Inhibitors / therapeutic use
-
Female
-
Gene Expression Regulation, Neoplastic / drug effects*
-
Histone Deacetylase Inhibitors / pharmacology*
-
Histone Deacetylase Inhibitors / therapeutic use
-
Humans
-
Mice
-
Mice, Nude
-
Promoter Regions, Genetic
-
Proto-Oncogene Proteins c-bcl-2 / genetics
-
Proto-Oncogene Proteins c-bcl-2 / metabolism
-
Transplantation, Heterologous
-
Valproic Acid / pharmacology
-
Valproic Acid / therapeutic use
Substances
-
Antineoplastic Agents
-
Cadherins
-
Enzyme Inhibitors
-
Histone Deacetylase Inhibitors
-
Proto-Oncogene Proteins c-bcl-2
-
Valproic Acid
-
Decitabine
-
DNA (Cytosine-5-)-Methyltransferases
-
Azacitidine