Hydralazine inhibits human cervical cancer cell growth in vitro in association with APC demethylation and re-expression

Abstract

Hydralazine, an effective inhibitor of APC methylation and promoter of APC re-expression, can inhibit cell growth in human cervical cancer in vitro and be potentially used for the clinical treatment of human cervical cancer.

Hypermethylation of promoter regions of the APC1A and p16INK4a genes in relation to prognosis and tumor characteristics in cervical cancer patients

“…The relationship we found between APC1A methylation status and clinical outcome in cervical cancer is in concordance with its function in cell adhesion and as an inactivator of β-catenin (7,8). This is supported by a recent in vitro study showing that demethylation of the APC promoter by hydralazin inhibited growth and increased β-catenin expression of the cervical cancer cell lines HeLa, CaSki and SiHa (41). Mechanistic models are also now being proposed (42,43) to account for the role and importance of APC1A in cell cycle regulation and adenoma formation.…”

Epigenetic Therapies for Cancer

“…Unlike the nucleoside analogues, procaine competes with DNMTs for binding to CpG rich regions (Jin et al, 2001). Procainamide and hydralazine are antiarrhythmic drugs that can also function as DNMTis, and both agents have been shown to inhibit DNA methylation through interactions between the nitrogen atom of procainamide and hydralazine with the lys-162 and Arg-240 moities in the catalytic site of DNMTs (Song et al, 2009;Singh et al, 2009;Mund et al, 2006). In accord with these findings, procainamide has been shown to specifically inhibit DNMT1 (Lee et al, 2005).…”

The Effect of Cytotoxic Dose of Diclofenac on APC Gene Expression in Cervical Cancer (Hela) Cell Line

“…It has been reported that frequent and long-term use of nonsteroidal anti-inflammatory drugs is associated with decreased odds of cervical cancer [11]. Increase in APC expression level also is associated with decreased risk of cancer [12][13][14][15][16].…”