TY - JOUR
T1 - Reactive oxygen species mediate arsenic induced cell transformation and tumorigenesis through Wnt/β-catenin pathway in human colorectal adenocarcinoma DLD1 cells
AU - Zhang, Zhuo
AU - Wang, Xin
AU - Cheng, Senping
AU - Sun, Lijuan
AU - Son, Young Ok
AU - Yao, Hua
AU - Li, Wenqi
AU - Budhraja, Amit
AU - Li, Li
AU - Shelton, Brent J.
AU - Tucker, Thomas
AU - Arnold, Susanne M.
AU - Shi, Xianglin
N1 - Funding Information:
This research is supported by NIH grants R01CA119028 , R01CA116697 , R01ES015375 , and R01ES015518 .
PY - 2011/10/15
Y1 - 2011/10/15
N2 - 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.
AB - 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.
KW - Arsenic
KW - Cell transformation
KW - NADPH oxidase
KW - Reactive oxygen species
KW - Tumorigenesis
KW - β-catenin
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U2 - 10.1016/j.taap.2011.07.016
DO - 10.1016/j.taap.2011.07.016
M3 - Article
C2 - 21854796
AN - SCOPUS:80053132303
SN - 0041-008X
VL - 256
SP - 114
EP - 121
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 2
ER -
