Cell Cycle Arrest and Apoptosis Induction by a New 2,4-Dinitrobenzenesulfonamide Derivative In Acute Leukemia Cells

Authors

  • Patricia Alves Almeida Federal University of Santa Catarina
  • Luiz Felipe Schmitz de Souza Federal University of Santa Catarina
  • Mariana Franzoni Maioral Federal University of Santa Catarina
  • Laura Otto Walter Federal University of Santa Catarina
  • Bruna Fischer Duarte Federal University of Santa Catarina
  • Íris Mattos Santos-Pirath Federal University of Santa Catarina
  • Douglas Bauer Speer Federal University of Santa Catarina
  • Larissa Sens Federal University of Santa Catarina
  • Tiago Tizziani Federal University of Santa Catarina
  • Aldo Sena de Oliveira Federal University of Santa Catarina
  • Ricardo José Nunes Federal University of Santa Catarina
  • Maria Cláudia Santos-Silva Federal University of Santa Catarina

DOI:

https://doi.org/10.18433/jpps31349

Abstract

Background: Current therapies for acute leukemias (ALs) are associated with severe adverse reactions and high relapse rates, which makes the search for new antileukemic agents a necessity. Therefore, the aim of this study was to evaluate the effects of a new sulfonamide, S1, in AL cells K562 and Jurkat. Methods: The cytotoxic activity of S1 was assessed using MTT method. The involvement of apoptosis in the mechanism of cell death was assessed by flow cytometry and fluorescence microscopy. Results: Our results demonstrated that S1 induced morphological changes suggestive of apoptosis in both K562 and Jurkat cells. Additionally, S1 was not cytotoxic to normal erythrocytes and mononuclear cells and had a highly selective cytotoxicity for AL lineages. The mechanisms of cell death induced by S1 in K562 cells involves cell cycle arrest at G2/M phase and the activation of both extrinsic and intrinsic apoptosis, with an increased FasR and AIF expression and the loss of mitochondrial potential. As for Jurkat, we observed cell cycle blockade at G0/G1 phase, phosphatidylserine exposure and the involvement of intrinsic apoptosis only, with mitochondrial potential loss and a reduced expression of Survivin.  Although sulfonamide S1 did not altered Bcl-2 and Bax expression in AL cell lines, it was able to activate caspase-3 in K562 cells. Conclusion: Our results suggest that sulfonamide S1 may be a promising candidate for the development of new drugs for the treatment of ALs

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Published

2021-01-15

How to Cite

Alves Almeida, P., Schmitz de Souza, L. F. ., Franzoni Maioral, M. ., Otto Walter, L., Fischer Duarte, B. ., Mattos Santos-Pirath, Íris ., Bauer Speer, D. ., Sens, L. ., Tizziani, T. ., Sena de Oliveira, A. ., Nunes, R. J. ., & Santos-Silva, M. C. . (2021). Cell Cycle Arrest and Apoptosis Induction by a New 2,4-Dinitrobenzenesulfonamide Derivative In Acute Leukemia Cells. Journal of Pharmacy & Pharmaceutical Sciences, 24, 23–36. https://doi.org/10.18433/jpps31349

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Section

Pharmaceutical Sciences; Original Research Articles