title: Acute application of cisplatin affects methylation status in neuroblastoma cells.
abstract: The pharmacological mechanism of the anti-cancer effect of cisplatin is well known to be DNA intercalation, but the direct or indirect effects of cisplatin on protein expression in cancer cells remain to be explained. In this study, we used a proteomic approach to clarify the early impact of cisplatin on protein expression. In a 2-dimensional gel electrophoresis proteomic experiment, the application of cisplatin for 24 h increased the expression of four proteins and decreased the levels of one protein in neuroblastoma IMR-32 cells. Levels of S-adenosyl-L-homocysteine hydrolase, a key enzyme in methylation metabolism, were increased the most. Therefore, we examined the methylation status of histone proteins. Histone H3K9 methylation was reduced by the application of cisplatin for 24 h. These results suggest that acute cisplatin treatment alters methylation status. Thus, these data can help clarify the unknown pharmacological mechanisms of cisplatin, including the anticancer effect, adverse effects and/or the mechanism of drug resistance.
authors.affiliation: Research Unit of Clinical Medicine, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan. tabata.keiichi@nihon-u.ac.jp
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tabata
authors.forename: Hayato
authors.initials: H
authors.lastname: Sakai
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Nakajima
authors.forename: Reiko
authors.initials: R
authors.lastname: Saya-Nishimura
authors.forename: Kou
authors.initials: K
authors.lastname: Motani
authors.forename: Soichiro
authors.initials: S
authors.lastname: Okano
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Shibata
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Abiko
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin