Sodium arsenite induces ROS generation, DNA oxidative damage, HO-1 and c-Myc proteins, NF-kappaB activation and cell proliferation in human breast cancer MCF-7 cells.
Epidemiological evidence has associated exposure to arsenic (As) in drinking water with an increased incidence of human cancers in the skin, bladder, liver, kidney and lung. Sodium arsenite mimics the effects of estradiol and induces cell proliferation in the estrogen responsive breast cancer cell line MCF-7. Therefore, our aim was to further explore the ability of sodium arsenite to induce MCF-7 epithelial breast cell proliferation and some of its underlying mechanisms by studying ROS production, c-Myc and HO-1 protein levels, 8-OHdG formation and NF-kappaB activation. Low arsenite concentrations (0.5-5 microM) induced ROS production and ROS-related depolarization of the mitochondrial membrane suggesting that mitochondria played an important role in the oxidative effects of As. ROS-mediated DNA damage as measured by the presence of 8-OHdG DNA-adducts in their nuclei, IkappaB phosphorylation, NF-kappaB activation and increases in c-Myc and HO-1 protein levels were also observed, suggesting that these factors play a relevant role in the arsenite induced MCF-7 cell recruitment into the S-phase of the cell cycle and cell proliferation observed. In conclusion, arsenite activates several pathways involved in MCF-7 cell proliferation suggesting that arsenite exposure may pose a risk for breast cancer in human exposed populations notwithstanding that most studies to date have not yet implicated this metalloid as a cofactor in the etiology of this disease.
Ruiz-Ramos
Ruben
R
Centro de Investigación en Salud Poblacional INSP, Cuernavaca, Morelos, Mexico.
Lopez-Carrillo
Lizbeth
L
Rios-Perez
Alfonso D
AD
De Vizcaya-Ruíz
Andrea
A
Cebrian
Mariano E
ME
D001149:Arsenates / Q000633:toxicity*; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018736:DNA Adducts / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D001149:Arsenates; D018736:DNA Adducts; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; C009277:sodium arsenate; D051547:Heme Oxygenase-1