Recently studies have shown that ectopic expression of activation-induced
cytidine deaminase (AID) plays an important role in carcinognesis and
cancer progression of inflammatory-associated
cancers. Here, we examined the molecular mechanism of ectopic expression of AID in
cancer cells, and whether or not
nitric oxide (NO) modulates this expression, as NO is known to cause chemical deamination of the
cytidine. In several
cancer cell lines, treatment with the
DNA methyltransferase (Dnmt) inhibitor 5-Aza-dC effected expression of AID by TNF-α, and expression was further induced by additional treatment with
histone deacetylase (
HDAC) inhibitors with no stimulation. The CpG sites located in the promoter and exon 1 region of the AID gene in
cancer cells were found to be hypomethylated in correlation with AID expression levels. Further, administration of
HDAC inhibitors also induced expression of
inducible nitric oxide synthase (iNOS) in
cancer cells treated with 5-Aza-dC. Interestingly, administration of S-nitroso-L-
glutathione (GSNO) a
nitric oxide (NO) donor, was found to enhance AID and iNOS expression in LoVo cells treated with 5-Aza-dC. Our findings suggest that AID and iNOS expression in
cancer cells may be modified by epigenetic mechanisms, and that NO may further enhance AID and iNOS expression. Given recent plans to introduce Dnmt and
HDAC inhibitors as novel
cancer treatments, these findings regarding the potential for Dnmt and
HDAC inhibitors to enhance expression of AID and iNOS, resulting in further
cancer progression, might be taken into consideration.