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Cytotoxic activity of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives in human breast cancer cells

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Abstract

Evaluation of the cytotoxicity of novel octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives (1a–2c) employing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and inhibition of [3H]thymidine incorporation into DNA demonstrated that these compounds were more active than etoposide and camptothecin in both MDA-MB-231 and MCF-7 human breast cancer cells. Flow cytometric analysis after Annexin V-FITC and propidium iodide staining also confirmed that apoptosis was the main response of human breast cancer cells to 1a–2c treatment. Our results suggest that apoptosis of human breast cancer cells in the presence of 1a–2c follows the mitochondrial pathway, with the decrease in mitochondrial membrane potential and activation of caspase 9, as well as by the external pathway with the significant increase in caspase 8 expression. Cytotoxic properties of compounds 1a–2c in cultured human breast cancer cells correlate to their ability to inhibit topoisomerase I/II.

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Acknowledgments

The authors are grateful to the National Science Centre (Grant DEC-2012/07/B/NZ7/04382) for financial support.

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The authors declare no conflict of interests.

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Authors and Affiliations

  1. Department of Biotechnology, Medical University of Białystok, Kilińskiego 1, 15-089, Białystok, Poland

    Monika Lepiarczyk, Anna Bielawska & Agnieszka Gornowicz

  2. Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland

    Zbigniew Kałuża

  3. Department of Synthesis and Technology of Drugs, Medical University of Białystok, Kilińskiego 1, 15-089, Białystok, Poland

    Robert Czarnomysy & Krzysztof Bielawski

Authors
  1. Monika Lepiarczyk
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  2. Zbigniew Kałuża
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  3. Anna Bielawska
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  4. Robert Czarnomysy
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  5. Agnieszka Gornowicz
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  6. Krzysztof Bielawski
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Correspondence to Krzysztof Bielawski.

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Lepiarczyk, M., Kałuża, Z., Bielawska, A. et al. Cytotoxic activity of octahydropyrazin[2,1-a:5,4-a′]diisoquinoline derivatives in human breast cancer cells. Arch. Pharm. Res. 38, 628–641 (2015). https://doi.org/10.1007/s12272-014-0444-z

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  • DOI: https://doi.org/10.1007/s12272-014-0444-z

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