title: Superoxide-hydrogen peroxide imbalance interferes with colorectal cancer cells viability, proliferation and oxaliplatin response.
abstract: The role of superoxide dismutase manganese dependent enzyme (SOD2) in colorectal cancer is presently insufficiently understood. Some studies suggest that high SOD2 levels found in cancer tissues are associated with cancer progression. However, thus far, the role of colorectal cancer superoxide-hydrogen peroxide imbalance has not yet been studied. Thus, in order to address this gap in extant literature, we performed an in vitro analysis using HT-29 colorectal cell line exposed to paraquat, which generates high superoxide levels, and porphyrin, a SOD2 mimic molecule. The effect of these drugs on colorectal cancer cell response to oxaliplatin was evaluated. At 0.1 μM concentration, both drugs exhibited cytotoxic and antiproliferative effect on colorectal cancer cells. However, this effect was more pronounced in cells exposed to paraquat. Paraquat also augmented the oxaliplatin cytotoxic and antiproliferative effects by increasing the number of apoptosis events, thus causing the cell cycle arrest in the S and M/G2 phases. The treatments were also able to differentially modulate genes related to apoptosis, cell proliferation and antioxidant enzyme system. However, the effects were highly variable and the results obtained were inconclusive. Nonetheless, our findings support the hypothesis that imbalance caused by increased hydrogen peroxide levels could be beneficial to cancer cell biology. Therefore, the use of therapeutic strategies to decrease hydrogen peroxide levels mainly during oxaliplatin chemotherapy could be clinically important to the outcomes of colorectal cancer treatment.
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Verônica Farina
authors.initials: VF
authors.lastname: Azzolin
authors.affiliation: Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Francine Carla
authors.initials: FC
authors.lastname: Cadoná
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Alencar Kolinski
authors.initials: AK
authors.lastname: Machado
authors.affiliation: Universidade Federal de Ciências da Saúde de Porto Alegre, Brazil.
authors.forename: Maiquidieli Dal
authors.initials: MD
authors.lastname: Berto
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Barbisan
authors.affiliation: Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Eduardo Bortoluzzi
authors.initials: EB
authors.lastname: Dornelles
authors.affiliation: BIOREP Lab, Centro de Ciências Agrárias, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Werner Giehl
authors.initials: WG
authors.lastname: Glanzner
authors.affiliation: BIOREP Lab, Centro de Ciências Agrárias, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Paulo Bayard
authors.initials: PB
authors.lastname: Gonçalves
authors.affiliation: Universidade Federal de Ciências da Saúde de Porto Alegre, Brazil.
authors.forename: Claudia Giugliano
authors.initials: CG
authors.lastname: Bica
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil; Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. Electronic address: ibmcruz@hotmail.com.
authors.forename: Ivana Beatrice Mânica
authors.initials: IB
authors.lastname: da Cruz
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D010269:Paraquat / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1 / Q000235:genetics; D000099156:Superoxide Dismutase 2
chemical_list: D000970:Antineoplastic Agents; D002374:Catalase; D005979:Glutathione Peroxidase; D006861:Hydrogen Peroxide; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010269:Paraquat; D011166:Porphyrins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human
keywords: Chemotherapy; HT-29 colorectal cell; Paraquat; Porphyrin; Superoxide dismutase manganese dependent