5-Aza-2'-deoxycytidine reactivates expression of RUNX3 by deletion of DNA methyltransferases leading to caspase independent apoptosis in colorectal cancer Lovo cells.

The DNA methylation inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR) has therapeutic value for the treatment of cancer. However, the mechanism by which 5-Aza-CdR induces antineoplastic activity is an important unresolved question. In this study, we found that 5-Aza-CdR at limited concentrations induced inhibition of colorectal cancer Lovo cell proliferation as well as increased apoptosis caused by DNA damage, which was independent of the caspase pathway. Regarding the mechanisms, for the first time, we examined that cytotoxicity against Lovo cells was regulated via down-regulation of DNA methyltransferase 3a, DNMT3b and then reactivated the expression of RUNX3. We therefore conclude that RUNX3 is a relevant target for methyltransferases dependent effects of 5-Aza-CdR on colorectal cancer Lovo cells.