Abstract 2634: Methionine metabolites specifically protect anticancer effect of 5-FU but not for cisplatin in human lung cancer cells

Abstract

Abstract It has been known that cellular methylation is associated with stabilization of chromatin structure. S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), as metabolites of methionine metabolism, are the substrate and end product of essential cellular methyltransferase reactions, respectively. In this study, we are to explain that these metabolites specifically regulate anticancer effect of 5-FU but not for cisplatin. Using MTT assay, we have found that combination treatment of SAM or SAH with 5-FU specifically protect the anticancer effect of 5-FU in time or dose dependent manner, whereas combination treatment with cisplatin had no effect. This result was also consistent in cell cycle distribution by FACS analysis. Induction of tumor suppressor p53 by anticancer drugs was decreased in combination treatment of those metabolites with 5-FU. We hypothesized what cellular methylation related proteins involve in the protection effect. SUV39H1 and G9a, typical HMTases for H3K9, also have no change in combination treatment of those metabolites with 5-FU. However, expression of DNMT3A and DNMT3B were increased at the combination treatment of SAM and 5-FU. Interestingly, there were no change on expression of DNMT3A and DNMT3B in combination treatment of SAH with 5-FU, indicating protection effect of SAM and SAH on 5-FU differently act at the molecular level. Together, we suggest that cellular methylation can specifically modulate anticancer effect of DNA damage agent 5-FU and this can be modulated by aberrant DNA methylation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2634. doi:10.1158/1538-7445.AM2011-2634