title: S-adenosyl methionine specifically protects the anticancer effect of 5-FU via DNMTs expression in human A549 lung cancer cells.
abstract: Cellular methylation is associated with stabilization of the chromatin structure. S-adenosyl methionine (SAM), a metabolite of methionine metabolism, is the methyl donor of essential cellular methyltransferase reactions. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-dephenyl tetrazolium bromide (MTT) assay, we found that combination treatment of SAM and 5-fluorouracil (5-FU) specifically protected the anticancer effect of 5-FU, whereas the combination of SAM and cisplatin had no effect. This result was confirmed by FACS analysis. The combination treatment of SAM and 5-FU significantly decreased the dead cell population, while the G1 cell population was slightly increased, suggesting that protection of SAM is not associated with the cell cycle arrest of DNA-damaging drugs. We also analyzed which cellular methylation-related proteins were involved in the protective effect. Results showed the expression of DNA methyltransferases (DNMTs) was decreased with 5-FU alone but was increased with the combination treatment of SAM and 5-FU, suggesting that SAM protects the anticancer effect of 5-FU by regulating the expression of DNMTs. Taken together, the results indicated that SAM specifically modulates the anti-cancer effect of the DNA damage agent 5-FU and this may be modulated by aberrant DNA methylation.
authors.affiliation: Medical and Bio-Material Research Center and Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Kangwon 200-701, Republic of Korea.
authors.forename: Myeong-Sun
authors.initials: MS
authors.lastname: Ham
authors.affiliation: Medical and Bio-Material Research Center and Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Kangwon 200-701, Republic of Korea.
authors.forename: Ju-Kyung
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Medical and Bio-Material Research Center and Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Kangwon 200-701, Republic of Korea.
authors.forename: Keun-Cheol
authors.initials: KC
authors.lastname: Kim
keywords: 5-fluorouracil; DNA methyltransferases; S-adenosyl methionine; cisplatin; protection