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In vitro evaluation of antitumoral efficacy of catalase in combination with traditional chemotherapeutic drugs against human lung adenocarcinoma cells

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Tumor Biology

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.

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Acknowledgments

Brazilians funds MCT/CNPq Universal (470306/2011-4), PRONEX/FAPERGS (1000274), PRONEM/FAPERGS (11/2032-5), PqG/FAPERGS (2414-2551/12-8), MCT/CNPq INCT-TM (573671/2008-7), and FAPERGS/MS/CNPq/SESRS/PPSUS (1121-2551/13-8) provided the financial support without interference in the ongoing work.

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Authors and Affiliations

  1. 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

    Valeska Aguiar de Oliveira, Leonardo Lisbôa da Motta, Marco Antônio De Bastiani, Fernanda Martins Lopes, Carolina Beatriz Müller, Bernardo Papini Gabiatti, Fernanda Stapenhorst França & Fabio Klamt

  2. National Institutes of Science & Technology – Translational Medicine (INCT-TM), 90035-903, Porto Alegre, RS, Brazil

    Valeska Aguiar de Oliveira, Leonardo Lisbôa da Motta, Marco Antônio De Bastiani, Fernanda Martins Lopes, Carolina Beatriz Müller, Mauro Antônio Alves Castro & Fabio Klamt

  3. Laboratory of Bioinformatics, Professional and Technological Education Sector, Centro Politécnico, UFPR, 81531-970, Curitiba, PR, Brazil

    Mauro Antônio Alves Castro

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  1. Valeska Aguiar de Oliveira
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  2. Leonardo Lisbôa da Motta
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de Oliveira, V.A., da Motta, L.L., De Bastiani, M.A. et al. In vitro evaluation of antitumoral efficacy of catalase in combination with traditional chemotherapeutic drugs against human lung adenocarcinoma cells. Tumor Biol. 37, 10775–10784 (2016). https://doi.org/10.1007/s13277-016-4973-6

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  • DOI: https://doi.org/10.1007/s13277-016-4973-6

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