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An in vitro comparative study with furyl-1,4-quinones endowed with anticancer activities

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Summary

We describe the biological activity of some furylbenzo- and naphthoquinones (furylquinones) on hepatocarcinoma cells and healthy rat liver slices. The effects of furylquinones on cancer cells (Transplantable Liver Tumor, TLT) were assessed by measuring cell death (membrane cell lysis); intracellular contents of ATP and GSH and the activity of caspase-3 were used to determine the type of cell death. Most of the furylquinones tested (at a concentration of 25 μg/ml) induced caspase-independent cell death but compound 4 had no cytotoxic effects. The levels of both ATP and GSH were severely affected by quinones 1, 2 and 5, while no effect was observed with compound 4. These cytotoxic properties of quinones are associated with physico-chemical properties as shown by the LUMO energies and lipophilicity. Interestingly, no cytotoxic effects of furylquinones were detected when the in vitro model of precision-cut liver slices (PCLS) was used. Indeed, although CYP2E1 activity was slightly affected, ATP and GSH levels as well as protein synthesis were not modified by furylquinones. Paracetamol, a well-known hepatotoxicant, reduced these parameters by more than 80% compared to control conditions. Taking into account the considerable incidence of adverse-effects induced by most current anticancer drugs, the selective cytotoxicity shown by compounds 1, 2 and 5, in particular that of 1, represents a safety factor that encourages the further development of these quinones as new drugs in cancer therapy.

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Acknowledgements

The authors express their gratitude to Isabelle Blave and Véronique Allaeys for their excellent technical assistance. Financial support by UNAP is gratefully acknowledged.

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Authors and Affiliations

  1. Departamento de Ciencias Químicas y Farmacéuticas, Universidad Arturo Prat, Iquique, Chile, Avenida Arturo Prat 2120, Casilla 121, Iquique, Chile

    Julio Benites & Pedro Buc Calderon

  2. Departamento Química Orgánica, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, Casilla 306, Santiago, Chile

    Jaime A. Valderrama

  3. Université Catholique de Louvain, Louvain Drug Research Institute, Toxicology and Cancer Biology Research Group, Unité PMNT 7369, 73, avenue E. Mounier, 1200, Brussels, Belgium

    Henryk Taper & Pedro Buc Calderon

  4. Instituto de EtnoFarmacologia (IDE), Universidad Arturo Prat, Iquique, Chile, Avenida Arturo Prat 2120, Casilla, 121, Iquique, Chile

    Julio Benites, Jaime A. Valderrama & Pedro Buc Calderon

Authors
  1. Julio Benites
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  2. Jaime A. Valderrama
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  3. Henryk Taper
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  4. Pedro Buc Calderon
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Corresponding author

Correspondence to Pedro Buc Calderon.

Additional information

In memoriam to Dr. Henry S. Taper who died on 24/04/2009

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Benites, J., Valderrama, J.A., Taper, H. et al. An in vitro comparative study with furyl-1,4-quinones endowed with anticancer activities. Invest New Drugs 29, 760–767 (2011). https://doi.org/10.1007/s10637-010-9419-1

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  • DOI: https://doi.org/10.1007/s10637-010-9419-1

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