期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 181, 期 2, 页码 175-184出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2009.06.019
关键词
Gallic acid derivatives; Apoptosis; Melanoma; Free radicals; NF-kappa B; Cell adhesion
资金
- CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
- CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
- FAPESC (Fundacao de Amparo a Pesquisa de Santa Catarina)
- Universidade do Contestado
Malignant melanoma is a lethal disease, and the incidence and mortality associated with it are increasing worldwide. It has a significant tendency to develop both metastasis and resistance to chemotherapy. The tumor cells show abnormal redox regulation, and although the molecular mechanisms involved are not well characterized, they seem to be related to oxidative stress. In a previous study, we showed the antitumoral properties of gallic acid ester derivatives in leukemia cells. Here, we show the effect of octyl, decyl, dodecyl and tetradecyl gallates on B16F10 cells, a melanoma cell line. All compounds induced cytotoxic effects, and the IC50 values obtained were between 7 mu M and 17 mu M after 48 h of incubation. Cell death occurred through apoptosis, as demonstrated by the genomic DNA fragmentation pattern. The gallates were able to induce significant production of free radicals, deplete both glutathione and ATP, activate NF-kappa B and promote the inhibition of cell adhesion under the experimental conditions. The glutathione depletion induced by these compounds was related to the inhibition of gamma-glutamylcysteine synthase activity. These results suggest that gallates induce tumoral cell death through apoptosis as a consequence of oxidative stress, though they use different mechanisms to do so. These findings are important since melanoma cells are resistant to death because of their high level of antioxidant defense, adhesion capability and propensity to metastasize. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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