title: Molecular changes during arsenic-induced cell transformation.
abstract: Arsenic and its derivatives are naturally occurring metalloid compounds widely distributed in the environment. Arsenics are known to cause cancers of the skin, liver, lung, kidney, and bladder. Although numerous carcinogenic pathways have been proposed, the exact molecular mechanisms remain to be delineated. To further characterize the role of oxidative stress in arsenite-induced cell transformation via the reactive oxygen species (ROS)-mediated Ras/Erk pathway, here we demonstrated arsenite-induced rat lung epithelial cell (LEC) transformation, epithelial-mesenchymal transition, stimulation of the extracellular signal-regulated kinase signaling pathway, and enhancement of cell proliferation. However, there was no evidence of activation of the phosphoinositide 3-kinase/protein kinase B pathway in arsenite-induced transformed LECs. Since ROS is involved in arsenite-induced LEC cell transformation, Redox-status regulatory proteins (Cu/Zn SOD and thioredoxin) and arsenite-induced LEC cell transformation were significantly inhibited by concurrent treatment with the antioxidants. Our experimental results clearly demonstrated that induction of p-ERK and cell proliferation by arsenite is mediated via oxidative stress, since antioxidants can inhibit arsenite-induced cell transformation.
authors.affiliation: Department of Biochemistry/Open Laboratory for Tumor Molecular Biology, Shantou University Medical College, Shantou, China.
authors.forename: Guanwu
authors.initials: G
authors.lastname: Li
authors.forename: Lai-Sheung
authors.initials: LS
authors.lastname: Lee
authors.forename: Muyao
authors.initials: M
authors.lastname: Li
authors.forename: Sai-Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Jen-Fu
authors.initials: JF
authors.lastname: Chiu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D018053:Arsenites / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D017670:Sodium Compounds / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018053:Arsenites; D002274:Carcinogens, Environmental; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; C017947:sodium arsenite; D013879:Thioredoxins; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; D018631:ras Proteins; D005978:Glutathione