title: Hypomethylation effects of curcumin, demethoxycurcumin and bisdemethoxycurcumin on WIF-1 promoter in non-small cell lung cancer cell lines.
abstract: The tumor suppressor gene Wnt inhibitory factor-1 (WIF-1) has been found to be promoter hypermethylated and silenced in lung cancer cell lines and tissues. Curcuminoids are major active components of the spice turmeric, and have recently been reported to be potential hypomethylation agents. In the present study, the hypomethylation effects of three major curcuminoids, curcumin, demethoxycurcumin and bisdemethoxycurcumin, were compared in vitro using ELISA, and their demethylation potential was confirmed by methylation-specific PCR. It was found that bisdemethoxycurcumin possesses the strongest demethylation function in vitro compared to the other two curcuminoids, exerting its effect at a minimal demethylation concentration of 0.5-1 µM. The WIF-1 promoter region was demethylated after treatment with 20 µM demethoxycurcumin and bisdemethoxycurcumin, but failed to respond to 20 µM curcumin. In the A549 cell line, RT-PCR and Western blotting were used to confirm that WIF-1 expression was restored after curcuminoid-induced promoter hypermethylation. Since the results regarding the demethylation potential of the three major curcuminoids to restore WIF-1 expression indicated that bisdemethoxycurcumin has the strongest hypomethylation effect, this curcuminoid may have therapeutic use in the restoration of WIF-1 expression in NSCLC.
authors.affiliation: Department of Respiratory Medicine, The Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Liu
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Gong
authors.forename: Chun-Lan
authors.initials: CL
authors.lastname: Tang
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects*; D036381:Diarylheptanoids; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D036381:Diarylheptanoids; D012097:Repressor Proteins; C485569:WIF1 protein, human; C034786:bisdemethoxycurcumin; D003474:Curcumin; C050229:demethoxycurcumin