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Research ArticleExperimental Studies

Phenothiazines and Selenocompounds: A Potential Novel Combination Therapy of Multidrug Resistant Cancer

MÁRIÓ GAJDÁCS, MÁRTA NOVÉ, ÁKOS CSONKA, BORISZ VARGA, CARMEN SANMARTÍN, ENRIQUE DOMÍNGUEZ-ÁLVAREZ and GABRIELLA SPENGLER
Anticancer Research September 2020, 40 (9) 4921-4928; DOI: https://doi.org/10.21873/anticanres.14495
MÁRIÓ GAJDÁCS
1Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary
2Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary
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MÁRTA NOVÉ
1Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary
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ÁKOS CSONKA
1Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary
3Department of Traumatology, Faculty of Medicine, University of Szeged, Szeged, Hungary
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BORISZ VARGA
1Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary
4Department of Rheumatology and Immunology, Szeged, Hungary
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CARMEN SANMARTÍN
5Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain
6Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
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ENRIQUE DOMÍNGUEZ-ÁLVAREZ
7Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas (IQOG-CSIC), Madrid, Spain
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GABRIELLA SPENGLER
1Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary
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  • For correspondence: spengler.gabriella@med.u-szeged.hu
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Abstract

Background/Aim: Phenothiazines constitute a versatile family of compounds in terms of biological activity, which have also gained a considerable attention in cancer research. Materials and Methods: Three phenothiazines (promethazine, chlorpromazine and thioridazine) have been tested in combination with 11 active selenocompounds against MDR (ABCB1-overexpressing) mouse T-lymphoma cells to investigate their activity as combination chemotherapy and as antitumor adjuvants in vitro with a checkerboard combination assay. Results: Seven selenocompounds showed toxicity on mouse embryonic fibroblasts, while three showed selectivity towards tumor cells. Two compounds showed synergism with all tested phenothiazines in low concentration ranges (1.46-11.25 μM). Thioridazine was the most potent among the three phenothiazines. Conclusion: Phenothiazines belonging to different generations showed different levels of adjuvant activities. All the tested phenothiazines are already approved medicines with known pharmacological and toxicity profiles, therefore, their use as adjuvants in cancer may be considered as a potential drug repurposing strategy.

  • Cancer
  • multidrug resistance
  • T-lymphoma
  • phenothiazines
  • selenoesters
  • selenoanhydride
  • combination chemotherapy
  • Received March 16, 2020.
  • Revision received March 27, 2020.
  • Accepted March 30, 2020.
  • Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
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Anticancer Research: 40 (9)
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Phenothiazines and Selenocompounds: A Potential Novel Combination Therapy of Multidrug Resistant Cancer
MÁRIÓ GAJDÁCS, MÁRTA NOVÉ, ÁKOS CSONKA, BORISZ VARGA, CARMEN SANMARTÍN, ENRIQUE DOMÍNGUEZ-ÁLVAREZ, GABRIELLA SPENGLER
Anticancer Research Sep 2020, 40 (9) 4921-4928; DOI: 10.21873/anticanres.14495

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Phenothiazines and Selenocompounds: A Potential Novel Combination Therapy of Multidrug Resistant Cancer
MÁRIÓ GAJDÁCS, MÁRTA NOVÉ, ÁKOS CSONKA, BORISZ VARGA, CARMEN SANMARTÍN, ENRIQUE DOMÍNGUEZ-ÁLVAREZ, GABRIELLA SPENGLER
Anticancer Research Sep 2020, 40 (9) 4921-4928; DOI: 10.21873/anticanres.14495
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Keywords

  • cancer
  • multidrug resistance
  • T-lymphoma
  • phenothiazines
  • selenoesters
  • selenoanhydride
  • combination chemotherapy
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