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.
Department of Internal Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei 430064, China. dengtao790601@yahoo.com.cn
Tao
T
Deng
Yan
Y
Zhang
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis*; D004249:DNA Damage; D000090205:DNA Methyltransferase 3A; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation; D006801:Humans
D000964:Antimetabolites, Antineoplastic; D050677:Core Binding Factor Alpha 3 Subunit; C000717967:DNMT3A protein, human; C493729:Runx3 protein, human; D000077209:Decitabine; D015254:DNA Modification Methylases; D000090205:DNA Methyltransferase 3A; D053148:Caspase 3; D001374:Azacitidine