title: Reactive oxygen species mediate arsenic induced cell transformation and tumorigenesis through Wnt/β-catenin pathway in human colorectal adenocarcinoma DLD1 cells.
abstract: Long term exposure to arsenic can increase incidence of human cancers, such as skin, lung, and colon rectum. The mechanism of arsenic induced carcinogenesis is still unclear. It is generally believed that reactive oxygen species (ROS) may play an important role in this process. In the present study, we investigate the possible linkage between ROS, β-catenin and arsenic induced transformation and tumorigenesis in human colorectal adenocarcinoma cell line, DLD1 cells. Our results show that arsenic was able to activate p47(phox) and p67(phox), two key proteins for activation of NADPH oxidase. Arsenic was also able to generate ROS in DLD1 cells. Arsenic increased β-catenin expression level and its promoter activity. ROS played a major role in arsenic-induced β-catenin activation. Treatment of DLD1 cells by arsenic enhanced both transformation and tumorigenesis of these cells. The tumor volumes of arsenic treated group were much larger than those without arsenic treatment. Addition of either superoxide dismutase (SOD) or catalase reduced arsenic induced cell transformation and tumor formation. The results indicate that ROS are involved in arsenic induced cell transformation and tumor formation possible through Wnt/β-catenin pathway in human colorectal adenocarcinoma cell line DLD1 cells.
authors.affiliation: Department of Preventive Medicine and Environmental Health, University of Kentucky, 121 Washington Avenue, Lexington, KY 40536, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Senping
authors.initials: S
authors.lastname: Cheng
authors.forename: Lijuan
authors.initials: L
authors.lastname: Sun
authors.forename: Young-Ok
authors.initials: YO
authors.lastname: Son
authors.forename: Hua
authors.initials: H
authors.lastname: Yao
authors.forename: Wenqi
authors.initials: W
authors.lastname: Li
authors.forename: Amit
authors.initials: A
authors.lastname: Budhraja
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Brent J
authors.initials: BJ
authors.lastname: Shelton
authors.forename: Thomas
authors.initials: T
authors.lastname: Tucker
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Arnold
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D015197:Carcinogenicity Tests; D051177:Catenins / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051153:Wnt Proteins / Q000187:drug effects / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D001152:Arsenicals; D051177:Catenins; D017382:Reactive Oxygen Species; D051153:Wnt Proteins; D051176:beta Catenin; D019255:NADPH Oxidases