Planta Med 2014; 80 - P1L18
DOI: 10.1055/s-0034-1394676

Evaluation of mutagenicity and metabolism-mediated cytotoxicity of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin from Paepalanthus latipes Silv., Eriocaulaceae

RR Kitagawa 1, R de Cassia Ribeiro Gonçalves 1, W Vilegas 2, E Varanda 3, MS Raddi 4
  • 1Department of Pharmaceutical Sciences, Federal University of Espírito Santo – UFES; Avenida Marechal Campos 1468, 29043 – 900 Vitória, ES, Brazil
  • 2Chemical Institute of Araraquara, Estadual Paulist University, UNESP, Rua Prof. Francisco Degni, s/n, PO Box 355, 14801 – 970 Araraquara, SP, Brazil
  • 3Department of Biological Sciences, Faculty of Pharmaceutical Sciences of Araraquara, Estadual Paulist University, UNESP, Rodovia Araraquara-Jaú, Km 1, PO Box 502, 14801 – 902 Araraquara, SP, Brazil
  • 4Department of Clinical Analysis, Faculty of Pharmaceutical Sciences of Araraquara, Estadual Paulist University, UNESP, Rua Expedicionários do Brasil, 1621 Araraquara, SP, Brazil

A large number of quinones have been associated with antitumor, antibacterial, antimalarial, and antifungal activities. Results of previous studies of 5-methoxy-3,4-dehydroxanthomegnin, a naphthoquinone isolated from Paepalanthus latipes, revealed antitumor, antibacterial, immunomodulatory, and antioxidant activities. In this study, we assessed the mutagenicity and metabolism-mediated cytotoxicity of 5-methoxy-3,4-dehydroxanthomegnin by using the Ames test and a microculture neutral red assay incorporating an S9 fraction (hepatic microsomal fraction and cofactors), respectively. We evaluated the mutagenic activity in Salmonella typhimurium strains TA100, TA98, TA102, and TA97a, as well as the cytotoxic effect on McCoy cells with and without metabolic activation in both tests. Results indicated that naphthoquinone does not cause mutations by substitution or by addition and deletion of bases in the DNA sequence with and without metabolic activation. As previously demonstrated, the in vitro cytotoxicity of 5-methoxy-3,4-dehydroxanthomegnin to McCoy cells showed a significant cytotoxic index (CI50) of 11.9 µg/mL. This index was not altered by addition of the S9 fraction, indicating that the S9 mixture failed to metabolically modify the compound. Our results, allied with more specific biological assays in the future, would contribute to the safe use of 5-methoxy-3,4-dehydroxanthomegnin, thereby signifying its beneficial properties as a potential anticancer drug.

Keywords: Cytotoxicity, 5-methoxy-3,4-dehydroxanthomegnin, mutagenicity, S9 fraction.

References:

Barile, F.A., 1994. Introduction to in vitro cytotoxicology: mechanisms and methods. Boca Raton: CRC Press, Inc.

Borenfreund, E., Puerner, J.A. 1987. Short-term quantitative in vitro cytotoxicity assay involving an S-9 activating system. Cancer Lett. 34, 243 – 248.

Kitagawa, R.R., Raddi, M.S.G., Santos, L.C., Vilegas, W. 2004. A new cytotoxic naphthoquinone from Paepalanthus latipes. Chem. Pharm. Bull. 52, 1487 – 1488.

Maron, D.M., Ames, B.N., 1983. Revised methods for the Salmonella mutagenicity test. Mutat. Res. 113, 173 – 225.