BACKGROUND: Histone deacetylase (HDAC) inhibitors are a group of small chemical 
molecules that inhibit histone deacetylase. At cell level, HDAC inhibitors have 
multiple biological effects such as cell cycle arrest, apoptosis, cell 
differentiation and auotophagy. At molecular level, HDAC inhibitors cause 
histone and nonhistone acetylation and induce gene expression. HDAC inhibitors 
are widely used in cancer therapy because of its function of inducing apoptosis. 
However, the mechanisms of apoptosis effect are not fully understood. TSA is a 
classical HDAC inhibitor and widely used in epigenetic and anti-cancer research. 
In this study, we selected Trichostatin A (TSA) to investigate the mechanisms of 
HDAC inhibitors apoptotic effect on cancer cells.
METHODS: Cervical cancer cell lines such as Hela, Caski and normal human 
keratinocyte line HaCaT were treated with various concentrations of TSA. Crystal 
violent assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide 
(MTT) assay were performed to determine cell number. PARP cleavage and 
FITC-AnexinV were performed to determine apoptosis. DNA-methyltransferase 
(DNMT)1, DNMT3A and DNMT3B were determined by regular PCR, qPCR and Western 
Blotting. Small interfering RNA (SiRNAi) was used to knock down DNMT3B.
RESULTS: HDAC inhibitors only induce cervical cancer cell apoptosis. At 1 µmol/L 
of TSA, 86% of Hela cell and 76% of Caski went apoptosis. For normal cells, HDAC 
inhibitors have no cytotoxic effect at therapeutic dosage, (90.0 ± 8.4)% of 
normal cell survive after treated with 1 µmol/L of TSA. We compared 1 µmol/L 
group with untreated control with t-test. There was no significance between 1 
µmol/L group and untreated control for normal cell (P > 0.05). HDAC inhibitors 
decreased DNMT3B in cancer cell but not in normal cell. Manually knock-down of 
DNMT3B induced Hela and Caski cell apoptosis. More than 99% of Hela and Caski 
cell went apoptosis after deprived of DNMT3B.
CONCLUSIONS: DNMT3B was essential to cervical cancer cell survival. 
Down-regulated DNMT3B by HDAC inhibitors may play an important role in the 
toxicity of HDAC inhibitors on cervical cancer cells.