tailieunhanh - Báo cáo y học: "Identification of novel DNA methylation inhibitors via a two-component reporter gene system"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Identification of novel DNA methylation inhibitors via a two-component reporter gene system | Lin et al. Journal of Biomedical Science 2011 18 3 http content 18 1 3 BIN sc The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Identification of novel DNA methylation inhibitors via a two-component reporter gene system 1 2 1 11 1 3 Yi-Shiuan Lin Arthur Y Shaw Shi-Gang Wang Chia-Chen Hsu I-Wen Teng Min-Jen Tseng Tim HM Huang Ching-Shih Chen4 Yu-Wei Leu 1 Shu-Huei Hsiao1 Abstract Background Targeting abnormal DNA methylation represents a therapeutically relevant strategy for cancer treatment as demonstrated by the US Food and Drug Administration approval of the DNA methyltransferase inhibitors azacytidine and 5-aza-2 -deoxycytidine for the treatment of myelodysplastic syndromes. But their use is associated with increased incidences of bone marrow suppression. Alternatively procainamide has emerged as a potential DNA demethylating agent for clinical translation. While procainamide is much safer than 5-aza-2 -deoxycytidine it requires high concentrations to be effective in DNA demethylation in suppressing cancer cell growth. Thus our laboratories have embarked on the pharmacological exploitation of procainamide to develop potent DNA methylation inhibitors through lead optimization. Methods We report the use of a DNA methylation two-component enhanced green fluorescent protein reporter system as a screening platform to identify novel DNA methylation inhibitors from a compound library containing procainamide derivatives. Results A lead agent IM25 which exhibits substantially higher potency in GSTpl DNA demethylation with lower cytotoxicity in MCF7 cells relative to procainamide and 5-aza-2 -deoxycytidine was identified by the screening platform. Conclusions Our data provide a proof-of-concept that procainamide could be pharmacologically exploited to develop novel DNA methylation inhibitors of which the translational potential in cancer therapy .