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Planta Med 1999; 65(6): 522-526
DOI: 10.1055/s-1999-14008
Original Paper

Georg Thieme Verlag Stuttgart · New York

Cytotoxicity of trans-Dehydrocrotonin from Croton cajucara on V79 Cells and Rat Hepatocytes

Jaime  A. Rodríguez1 , Marcela Haun2
  • 1 Instituto de Biologia Vegetal y Biotecnología, Universidad de Talca, Talca, Chile
  • 2 Departamento de Bioquímica, Instituto de Biología, Universidade Estadual de Campinas, Campinas São Paulo, Brasil
Further Information

Publication History

November 22, 1998

March 25, 1999

Publication Date:
31 December 1999 (online)

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Abstract

The cytotoxicity of trans-dehydrocrotonin (DHC), an antiulcerogenic diterpene from Croton cajucara (Euphorbiaceae), was assessed on a V79 fibroblast cell line and on rat hepatocytes. Three independent endpoints for cytotoxicity were evaluated: DNA content, MTT reduction and neutral red uptake (NRU). For the V79 cells IC50 values of 253 and 360 μM were obtained for the NRU and MTT tests. The cytotoxic effect of DHC was time exposure dependent and no ability to recover after treatment was observed. For the rat hepatocytes IC50 values of 8, 300 and 400 μM for the MTT, DNA and NRU assays were obtained. The greater toxicity observed for the MTT test was inhibited when the experiment was performed using non-fresh hepatocytes in an age-dependent fashion. The treatment of V79 cells with the conditioned medium resulting after hepatocyte incubation with DHC showed an enhancement of MTT reduction without any evident toxic effects on fibroblasts. These results suggest that DHC has basal cytotoxic effects as observed on V79 fibroblasts and expresses a selective cytotoxicity after its metabolization by the hepatocytes. The bioactivation of DHC is mediated by cytochrome P450 and could generate metabolites that have no toxicity for V79 fibroblasts.

Key words:

Croton cajucara - Euphorbiaceae - trans-dehydrocrotonin - cytotoxicty - V79 cells - hepatocytes