Vorinostat (suberoylanilide hydroxamic acid), a class of histone deacetylase 
inhibitors, represents an emerging class of anticancer agents currently 
progressing in clinical trials. It causes cell growth inhibition, 
differentiation, and apoptosis of many tumor types in vitro and in vivo. 
Recently, it was reported that hTERT is one of the targets for cancer therapy in 
cancer cells. Telomerase repeat amplification protocol assay was used to analyze 
the expression of hTERT after vorinostat treatment in the A549 lung cancer 
cells. Vorinostat inhibited telomerase activity by reducing the expression of 
human telomerase reverse transcriptase (hTERT) in A549 human lung cancer cells. 
The epigenetic regulation mechanism is responsible for the repression of hTERT 
by vorinostat, analyzed through the methylation-specific PCR and bisulfite 
sequencing of the hTERT promoter. Vorinostat induced the demethylation of 
site-specific CpGs on the promoter region of hTERT, which was caused by the 
down-regulation of DNA methyltransferases. DNA methyltransferases (DNMT1 and 
DNMT3b) were also decreased in vorinostat-treated A549 cancer cells. 
Furthermore, chromatin immunoprecipitation analysis of the hTERT promoter 
revealed that vorinostat decreased the level of inactive chromatin markers 
dimethyl-H3K9, and the declined binding of DNMT1 and DNMT3b were associated. The 
novel insights showed that vorinostat down-regulated telomerase via epigenetic 
alteration in lung cancer to vorinostat-mediated cancer-specific therapies.