title: In vitro evaluation of antitumoral efficacy of catalase in combination with traditional chemotherapeutic drugs against human lung adenocarcinoma cells.
abstract: Lung cancer is the most lethal cancer-related disease worldwide. Since survival rates remain poor, there is an urgent need for more effective therapies that could increase the overall survival of lung cancer patients. Lung tumors exhibit increased levels of oxidative markers with altered levels of antioxidant defenses, and previous studies demonstrated that the overexpression of the antioxidant enzyme catalase (CAT) might control tumor proliferation and aggressiveness. Herein, we evaluated the effect of CAT treatment on the sensitivity of A549 human lung adenocarcinoma cells toward various anticancer treatments, aiming to establish the best drug combination for further therapeutic management of this disease. Exponentially growing A549 cells were treated with CAT alone or in combination with chemotherapeutic drugs (cisplatin, 5-fluorouracil, paclitaxel, daunorubicin, and hydroxyurea). CalcuSyn(®) software was used to assess CAT/drug interactions (synergism or antagonism). Growth inhibition, NFκB activation status, and redox parameters were also evaluated in CAT-treated A549 cells. CAT treatment caused a cytostatic effect, decreased NFκB activation, and modulated the redox parameters evaluated. CAT treatment exhibited a synergistic effect among most of the anticancer drugs tested, which is significantly correlated with an increased H2O2 production. Moreover, CAT combination caused an antagonism in paclitaxel anticancer effect. These data suggest that combining CAT (or CAT analogs) with traditional chemotherapeutic drugs, especially cisplatin, is a promising therapeutic strategy for the treatment of lung cancer.
authors.affiliation: Laboratory of Cellular Biochemistry, Departamento de Bioquímica, ICBS/ Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, Porto Alegre, RS, 90035-003, Brazil.|National Institutes of Science & Technology - Translational Medicine (INCT-TM), 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Valeska Aguiar
authors.initials: VA
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Cellular Biochemistry, Departamento de Bioquímica, ICBS/ Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, Porto Alegre, RS, 90035-003, Brazil.|National Institutes of Science & Technology - Translational Medicine (INCT-TM), 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Leonardo Lisbôa
authors.initials: LL
authors.lastname: da Motta
authors.affiliation: Laboratory of Cellular Biochemistry, Departamento de Bioquímica, ICBS/ Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, Porto Alegre, RS, 90035-003, Brazil.|National Institutes of Science & Technology - Translational Medicine (INCT-TM), 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Marco Antônio
authors.initials: MA
authors.lastname: De Bastiani
authors.affiliation: Laboratory of Cellular Biochemistry, Departamento de Bioquímica, ICBS/ Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, Porto Alegre, RS, 90035-003, Brazil.|National Institutes of Science & Technology - Translational Medicine (INCT-TM), 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Fernanda Martins
authors.initials: FM
authors.lastname: Lopes
authors.affiliation: Laboratory of Cellular Biochemistry, Departamento de Bioquímica, ICBS/ Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, Porto Alegre, RS, 90035-003, Brazil.|National Institutes of Science & Technology - Translational Medicine (INCT-TM), 90035-903, Porto Alegre, RS, Brazil.
authors.forename: Carolina Beatriz
authors.initials: CB
authors.lastname: Müller
authors.affiliation: Laboratory of Cellular Biochemistry, Departamento de Bioquímica, ICBS/ Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Bernardo Papini
authors.initials: BP
authors.lastname: Gabiatti
authors.affiliation: Laboratory of Cellular Biochemistry, Departamento de Bioquímica, ICBS/ Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Fernanda Stapenhorst
authors.initials: FS
authors.lastname: França
authors.affiliation: National Institutes of Science & Technology - Translational Medicine (INCT-TM), 90035-903, Porto Alegre, RS, Brazil.|Laboratory of Bioinformatics, Professional and Technological Education Sector, Centro Politécnico, UFPR, 81531-970, Curitiba, PR, Brazil.
authors.forename: Mauro Antônio Alves
authors.initials: MA
authors.lastname: Castro
authors.affiliation: Laboratory of Cellular Biochemistry, Departamento de Bioquímica, ICBS/ Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, Porto Alegre, RS, 90035-003, Brazil. 00025267@ufrgs.br.|National Institutes of Science & Technology - Translational Medicine (INCT-TM), 90035-903, Porto Alegre, RS, Brazil. 00025267@ufrgs.br.
authors.forename: Fabio
authors.initials: F
authors.lastname: Klamt
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019803:Glutathione Disulfide / Q000032:analysis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy*; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D009363:Neoplasm Proteins; D013438:Sulfhydryl Compounds; D006861:Hydrogen Peroxide; D002374:Catalase; D019803:Glutathione Disulfide
keywords: A549 cells; Anticancer drug combination; Catalase; Chemotherapy; Drug synergism; Lung cancer