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Tumor Biology

, Volume 37, Issue 8, pp 10775–10784 | Cite as

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

  • Valeska Aguiar de Oliveira
  • Leonardo Lisbôa da Motta
  • Marco Antônio De Bastiani
  • Fernanda Martins Lopes
  • Carolina Beatriz Müller
  • Bernardo Papini Gabiatti
  • Fernanda Stapenhorst França
  • Mauro Antônio Alves Castro
  • Fabio Klamt
Original Article

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.

Keywords

Lung cancer A549 cells Catalase Anticancer drug combination Chemotherapy Drug synergism 

Notes

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.

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

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Supplementary Fig. 1

(GIF 434 kb)

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High resolution image (TIFF 2.85 mb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Valeska Aguiar de Oliveira
    • 1
    • 2
  • Leonardo Lisbôa da Motta
    • 1
    • 2
  • Marco Antônio De Bastiani
    • 1
    • 2
  • Fernanda Martins Lopes
    • 1
    • 2
  • Carolina Beatriz Müller
    • 1
    • 2
  • Bernardo Papini Gabiatti
    • 1
  • Fernanda Stapenhorst França
    • 1
  • Mauro Antônio Alves Castro
    • 2
    • 3
  • Fabio Klamt
    • 1
    • 2
  1. 1.Laboratory of Cellular Biochemistry, Departamento de BioquímicaICBS/ Universidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  2. 2.National Institutes of Science & Technology – Translational Medicine (INCT-TM)Porto AlegreBrazil
  3. 3.Laboratory of BioinformaticsProfessional and Technological Education Sector, Centro Politécnico, UFPRCuritibaBrazil

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