Effect of Sodium Arsenite on the Expression of Antioxidant Genes (SOD2 and CAT) in MCF-7 and Jurkat Cell Lines
AbstractBackground: Sodium arsenite (NaAsO2) has potent cytotoxic activity in human cancer cells. Oxidative stress has been suggested as a mechanism for arsenic-induced carcinogenesis. The purpose of the present study was to evaluate the alteration of mRNA levels of catalase (CAT) and superoxide dismutase 2 (SOD2) in MCF-7 and Jurkat cells after exposure to NaAsO2.Methods: Methylthiazol tetrazolium (MTT) viability assay was performed to evaluate cytotoxicity of NaAsO2 in MCF-7 and Jurkat cells. For evaluating the expression levels of the CAT and SOD2, we used two concentrations of NaAsO2 (5 and 15 µM), lower than the concentrations at which 50% of cell viability were lost. The cells were treated with co-treatment of NaAsO2 (15 µM) and N-acetyl-cysteine (NAC; 5 µM) in the media for 24 h. The control cells were maintained in sodium arsenite free growth medium. The experiments were done triplicate. Using quantitative real-time PCR, the expression levels of CAT and SOD2 were quantified. One sample student’s t test was performed for comparisons of mRNA levels between treatment groups and their corresponding untreated control cells.Results: CAT mRNA level decreased significantly in both cell lines following exposure to NaAsO2 (P<0.05). Expression levels of SOD2 decreased in Jurkat cells and increased in MCF-7 cells after treatment with NaAsO2 (P<0.05).Conclusion: After cells exposure to NaAsO2, CAT mRNA level decreased in both examined cell lines but the alterations of SOD2 mRNA level is cell specific. The NAC modulated the NaAsO2 associated alterations of CAT and SOD2 mRNA levels, therefore, the NaAsO2 might act through inducing reactive oxygen species.
Navarro Silvera SA, Rohan TE (2007). Trace ele-ments and cancer risk: a review of the epidemio-logic evidence. Cancer Causes Control, 18:7-27.
Masoudi M, Saadat M (2008). Arsenic, GSTO2 Asn142Asp polymorphism, health, and treat-ment. EXCLI J, 7:115-8.
Kapaj S, Peterson H, Liber K, Bhattacharya P (2006). Human health effects from chronic arsenic poi-soning: a review. J Environ Sci Health A Tox Hazard Subst Environ Eng, 41:2399-428.
Lynn S, Gurr JR, Lai HT, Jan KY (2000). NADH oxidase activation is involved in arsenite-induced oxidative DNA damage in human vascular smooth muscle cells. Circ Res, 86:514-9.
Iwama K, Nakajo S, Aiuchi T, Nakaya K (2001). Apoptosis induced by arsenic trioxide in leukemia U937 cells is dependent on activation of p38, in-activation of ERK and the Ca2+-dependent production of superoxide. Int J Cancer, 92:518-26.
Liu SX, Athar M, Lippai I, Waldren C, Hei TK (2001). Induction of oxyradicals by arsenic: impli-cation for mechanism of genotoxicity. Proc Natl Acad Sci U S A, 98: 1643-8.
Shi H, Shi X, Liu KJ (2004). Oxidative mechanism of arsenic toxicity and carcinogenesis. Mol Cell Biochem, 255:67-78.
Wang TS, Shu YF, Liu YC, Jan KY, Huang H (1997). Glutathione peroxidase and catalase modulate the genotoxicity of arsenite. Toxicology, 121:229-37.
Yih LH, Peck K, Lee TC (2002). Changes in gene expression profiles of humans fibroblasts in response to sodium arsenite treatment. Carcinogenesis, 23:867-76.
Shrivastav M, De Haro LP, Nickoloff JA (2008). Regulation of DNA double-strand break repair pathway choice. Cell Res, 18:134-47.
Sedigh-Ardekani M, Saadat I, Saadat M (2013). Pro-pranolol induced chromosomal aberrations in Chinese hamster ovary cell line. Mol Biol Res Com-mun, 2:11-8.
Sedigh-Ardekani M, Saadat I, Saadat M (2014). Eval-uation of chromosomal aberrations induced by hydralazine in Chinese hamster ovary cells. Egypt J Med Hum Genet, 15:343-6.
Saadat I, Saadat M (2013). Effect of sodium arsenite on the expression of GSTM1, GSTT1 and GSTO2. Comp Clin Path, 22:1061-3.
Suzuki S, Arnold LL, Pennington KL, Kakiuchi-Kiyota S, Cohen SM (2009). Effects of co-administration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium. Toxicology, 261:41-6.
Khodayari S, Salehi Z, Fakhrieh Asl S, Aminian K, Mirzaei Gisomi N, Torabi Dalivandan S (2013). Catalase gene C-262T polymorphism: im-portance in ulcerative colitis. J Gastroenterol Hepatol, 28:819-22.
Ebrahimpour S, Saadat I (2014). Association of CAT C-262T and SOD1 A251G single nucleotide pol-ymorphisms susceptible to gastric cancer. Mol Biol Res Commun, 3:223-9.
Saadat M, Safaie S, Saadat I (2014). Genetic polymor-phism of C-262T catalase and susceptibility to schizophrenia. Maced J Med Sci, 2:74-7.
Saadat M, Saadat S (2015). Genetic polymorphism of CAT C-262 T and susceptibility to breast cancer, a case-control study and meta-analysis of the litera-tures. Pathol Oncol Res, 21:433-7.
Hernandez-Saavedra D, McCord JM (2009). Associ-ation of a new intronic polymorphism of the SOD2 gene (G1677T) with cancer. Cell Biochem Funct, 27: 223-7.
Xu Z, Zhu H, Luk JM, Wu D, Gu D, Gong W, Tan Y, Zhou J, Tang J, Zhang Z, Wang M, Chen J (2012). Clinical significance of SOD2 and GSTP1 gene polymorphisms in Chinese patients with gastric cancer. Cancer, 118:5489-96.
Liu Y, Zha L, Li B, Zhang L, Yu T, Li L (2014). Cor-relation between superoxide dismutase 1 and 2 polymorphisms and susceptibility to oral squa-mous cell carcinoma. Exp Ther Med, 7:171-8.
Saify K, Saadat M (2015). Expression patterns of an-tioxidant genes in human SH-SY5Y cells after treatment with methadone. Psychiatry Res, 230:116-9.
Saify K, Saadat I, Saadat M (2016). Down-regulation of antioxidant genes in human SH-SY5Y cells af-ter treatment with morphine. Life Sci, 144:26-9.
Argos M, Kibriya MG, Parvez F, Jasmine F, Rakibuz-Zaman M, Ahsan H (2006). Gene expression profiles in peripheral lymphocytes by arsenic ex-posure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev, 15: 1367-75.
Hemalatha P, Reddy AG, Reddy YR, Shivakumar P (2013). Evaluation of protective effect of N-acetyl cysteine on arsenic-induced hepatotoxicity. J Nat Sci Biol Med, 4:393-5.
Kim Y, Jeong IG, You D, Song SH, Suh N, Jang SW, Kim S, Hwang JJ, Kim CS (2014). Sodium meta-arsenite induces reactive oxygen species-dependent apoptosis, necrosis, and autophagy in both androgen-sensitive and androgen-insensitive prostate cancer cells. Anticancer Drugs, 25:53-62.
Sun X, Li B, Li X, Wang Y, Xu Y, Jin Y, Piao F, Sun G (2006). Effects of sodium arsenite on catalase activity, gene and protein expression in HaCaT cells. Toxicol In Vitro, 20:1139-44.
Jain A, Yadav A, Bozhkov AI, Padalko VI, Flora SJ (2011). Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats. Ecotoxicol Environ Saf, 74:607-14.
Shi Y, Wei Y, Qu S, Wang Y, Li Y, Li R (2010). Ar-senic induces apoptosis of human umbilical vein endothelial cells through mitochondrial pathways. Cardiovasc Toxicol, 10:153-60.
Reddy PS, Rani GP, Sainath SB, Meena R, Supriya Ch (2011). Protective effects of N-acetyl-cysteine against arsenic-induced oxidative stress and repro-toxicity in male mice. J Trace Elem Med Biol, 25:247-53.
Johnson AD, Zhang Y, Papp AC, Pinsonneault JK, Lim JE, Saffen D, Dai Z, Wang D, Sadée W (2008). Polymorphisms affecting gene transcrip-tion and mRNA processing in pharmacogenetic candidate genes: detection through allelic expres-sion imbalance in human target tissues. Pharmaco-genet Genomics, 18:781-91.
Ribeiro G, Roehrs M, Bairros A, Moro A, Charão M, Araújo F, Valentini J, et al. (2011). N-acetylcysteine on oxidative damage in diabetic rats. Drug Chem Toxicol, 34:467-74.
de Andrade KQ, Moura FA, Dos Santos JM, de Araújo OR, de Farias Santos JC, Goulart MO (2015). Oxidative stress and inflammation in he-patic diseases: Therapeutic possibilities of N-acetylcysteine. Int J Mol Sci, 16:30269-308.