Nutritional shortage augments cisplatin-effects on murine melanoma cells

Autor(es)

Antunes, F. ^[1] ; Pereira, G. J. ^[1] ; Jasiulionis, M. G. ^[1] ; Bincoletto, C. ^[1] ; Smaili, S. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, EPM, Dept Pharmacol, UNIFESP, Rua Tres Maio 100, BR-04044020 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Chemico-Biological Interactions; v. 281, p. 89-97, FEB 1 2018.
• Citações Web of Science: 3

Resumo

Melanoma incidence increases every year worldwide and is responsible for 80% of skin cancer deaths. Due to its metastatic potential and resistance to almost any treatments such as chemo, radio, immune and targeted-therapy, the patients still have a poor prognosis, especially at metastatic stage. Considering that, it is crucial to find new therapeutic approaches to overcome melanoma resistance. Here we investigated the effect of cisplatin (CDDP), one of the chemotherapeutic agents used for melanoma treatment, in association with nutritional deprivation in murine melanoma cell lines. Cell death and autophagy were evaluated after the treatment with cisplatin, nutritional deprivation and its association using an in vitro model of murine melanocytes malignant transformation to metastatic melanoma. Our results showed that nutritional deprivation augmented cell death induced by cisplatin in melanoma cells, especially at the metastatic subtype, with slight effects on melanocytes. Mechanistic studies revealed that although autophagy was present at high levels in basal conditions in melanoma cells, was not essential for cell death process that involved mitochondrial damage, reactive oxygen species production and possible glycolysis inhibition. In conclusion, nutritional shortage in combination with chemotherapeutic drugs as cisplatin can be a valuable new therapeutic strategy to overcome melanoma resistance. (AU)

• Processo FAPESP: 12/51215-4 - Autofagia e glicogênio sintase quinase-3 (GSK3) como alvos moleculares capazes de aumentar a atividade de fármacos utilizados no tratamento de leucemias mielóides (aguda e crônica)
• Beneficiário: Claudia Bincoletto Trindade
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/20073-2 - Estudo da autofagia no processo de proteção celular de ratas senescentes
• Beneficiário: Soraya Soubhi Smaili
• Modalidade de apoio: Auxílio à Pesquisa - Regular