Combination of omega-3 fatty acids and cisplatin as a potential alternative strategy for personalized therapy of metastatic melanoma: an in-vitro study

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art_VASCONCELOS_Combination_of_omega3_fatty_acids_and_cisplatin_as_2019.PDF (556.56 KB)
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2019
Editora
LIPPINCOTT WILLIAMS & WILKINS
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
SERINI, Simona
VOTTO, Ana Paula de Souza
TRINDADE, Gilma Santos
FANALI, Caterina
SGAMBATO, Alessandro
CALVIELLO, Gabriella
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
MELANOMA RESEARCH, v.29, n.3, p.270-280, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
The recently developed therapeutic strategies have led to unprecedented improvements in the control of metastatic melanoma and in the survival of specific subgroups of patients. However, drug resistance, low response rates, and undesired side effects make these treatments not suitable or tolerable for all the patients, and chemotherapeutic treatments appear still indispensable, at least for subgroups of patients. New combinatory strategies are also under investigation as tailored treatments or salvage therapies, including combined treatments of immunotherapy with conventional chemotherapy. On this basis, and in consideration of the antineoplastic properties of omega-3 polyunsaturated fatty acids, we have here investigated the potential of these bioactive dietary factors to revert the resistance frequently exhibited by this form of cancer to cisplatin (CDDP, cis-diamminedichloroplatinum). We demonstrated that docosahexenoic acid (DHA, 22:6 omega-3) sensitizes the cells to the CDDP-induced inhibition of cell growth and migration by reverting CDDP effects on DNA damage and ERCC1 expression, as well as on the DUSP6 and p-ERK expressions, which regulate ERCC1 activation upwardly. In line, DUSP6 gene silencing prevented the effect of DHA, confirming that DHA acted on the DUSP6/p-ERK/ERCC1 repair pathways to sensitize melanoma cells to the anticancer effect of CDDP. Similar effects were obtained also with eicosapentaenoic acid (20:5 omega-3). Overall, our findings suggest that the combination of CDDP treatment with a dietary supplementation with omega-3 polyunsaturated fatty acids could potentially represent a new therapeutic strategy for overcoming CDDP resistance in metastatic melanoma.
Palavras-chave
cisplatin, combinatory strategies, DUSP6, ERCC1, metastatic melanoma, pERK1, 2, personalized medicine, omega-3 PUFAs, resistance
URI
https://observatorio.fm.usp.br/handle/OPI/31829
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Coleções
Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03