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Octyl and dodecyl gallates induce oxidative stress and apoptosis in a melanoma cell line

2011; Elsevier BV; Volume: 25; Issue: 8 Linguagem: Inglês

10.1016/j.tiv.2011.08.003

1879-3177

Clarissa Amorim Silva de Cordova, Claudriana Locatelli, Laura S. Assunção, Bruno Mattei, Alessandra Mascarello, Evelyn Winter, Ricardo J. Nunes, Rosendo Augusto Yunes, Tânia Beatriz Creczynski‐Pasa,

Curcumin's Biomedical Applications

This study investigated the mechanism of cytotoxicity of octyl (G8) and dodecyl (G12) gallates in a murine melanoma cell line (B16F10). For this purpose, several methods to measure cell viability were used to determine if the cytotoxicity induced by these gallates corresponds to a general or an organelle-specific effect. Furthermore, the mechanisms related to apoptosis were examined, by studying the caspase-3 activity, oxidative stress, mitochondrial potential and the expression of anti- or proapoptotic proteins. When comparing the various methods of assessing cell viability, the tested gallates showed a higher cytotoxicity in the assay that indicates lysosomal activity, compared with the assays that indicate mitochondrial and ribosomal activities. Both gallates promoted the release of lactate dehydrogenase into the medium, indicating an effect on cell membrane integrity. The gallates also promoted cellular oxidative stress, mitochondrial depolarization and an increase in caspase-3 activity. Furthermore, the gallates induced an increase in proapoptotic (Bax) and a decrease in antiapoptotic (Bcl-2) proteins expression. Our results indicate that the apoptotic cell death induced by G8 and G12 in B16F10 cells involves lipid membrane damages, lysosomal and mitochondrial dysfunction, which was accompanied by alterations in apoptotic proteins expression and seems to be triggered by cellular oxidative stress.