Procaine inhibits the proliferation and DNA methylation in human hepatoma cells.

Abstract:

PURPOSE:Transcriptional silencing of tumor suppressor genes associated with DNA hypermethylation has been known as a hallmark of human cancer. In this study, we revealed that a local anesthetic, procaine (PCA), possessed growth-inhibitory and demethylating effect on human hepatoma cells in vitro and in vivo. METHODS:The viability of PCA-treated cells with or without trichostatin A (TSA) was investigated. To clarify the mechanism of the antiproliferating effect of PCA, TUNEL assay, FACS analysis, and morphological observation of PCA-treated cells were performed. The expression levels and epigenetic alterations of 4 genes inactivated by DNA hypermethylation in hepatocellular carcinoma (HCC) were examined in hepatoma cells with or without PCA treatment. The growth-inhibitory and demethylating effect of PCA in vivo was tested in nude mice bearing xenograft. RESULTS:The viability of HLE, HuH7, and HuH6 cells was significantly decreased by PCA treatment. In these cells, the combination treatment with TSA and PCA exhibited stronger reduction of the viability. Inhibition of S/G2/M transition, morphological changes such as vacuolation and no increase in apoptosis rate were observed in the PCA-treated HLE cells. All the genes transcriptionally suppressed by DNA hypermethylation were demethylated and reactivated with PCA treatment. PCA treatment led to partial demethylation and significant reduction in tumor volume in vivo. CONCLUSIONS:These data indicated that PCA had growth-inhibitory and demethylating effects on human hepatoma cells in vitro and in vivo. PCA may be a candidate agent for future therapies for HCC.

journal_name

Hepatol Int

journal_title

Hepatology international

authors

Tada M,Imazeki F,Fukai K,Sakamoto A,Arai M,Mikata R,Tokuhisa T,Yokosuka O

doi

10.1007/s12072-007-9014-5

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

355-64

issue

3

eissn

1936-0533

issn

1936-0541

journal_volume

1

pub_type

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