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Violacein induces death of RAS-mutated metastatic melanoma by impairing autophagy process.
Gonçalves, Paola R; Rocha-Brito, Karin J P; Fernandes, Maruska R N; Abrantes, Julia L; Durán, Nelson; Ferreira-Halder, Carmen V.
Afiliação
  • Gonçalves PR; Departamento de Ciências da Saúde, Centro Universitário Norte do Espírito Santo, Universidade Federal do Espírito Santo, São Mateus, Espírito Santo, Brazil.
  • Rocha-Brito KJ; Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
  • Fernandes MR; Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
  • Abrantes JL; Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
  • Durán N; Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
  • Ferreira-Halder CV; Institute of Chemistry, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
Tumour Biol ; 37(10): 14049-14058, 2016 Oct.
Article em En | MEDLINE | ID: mdl-27502397
Treatment of metastatic melanoma still remains a challenge, since in advanced stage it is refractory to conventional treatments. Most patients with melanoma have either B-RAF or N-RAS mutations, and these oncogenes lead to activation of the RAS-RAF-MEK-ERK and AKT signal pathway, keeping active the proliferation and survival pathways in the cell. Therefore, the identification of small molecules that block metastatic cell proliferation and induce cell death is needed. Violacein, a pigment produced by Chromobacterium violaceum found in Amazon River, has been used by our group as a biotool for scrutinizing signaling pathways associated with proliferation, survival, aggressiveness, and resistance of cancer cells. In the present study, we demonstrate that violacein diminished the viability of RAS- and RAF-mutated melanoma cells (IC50 value ∼500 nM), and more important, this effect was not abolished after treatment medium removal. Furthermore, violacein was able to reduce significantly the invasion capacity of metastatic melanoma cells in 3D culture. In the molecular context, we have shown for the first time that violacein causes a strong drop on histone deacetylase 6 expression, a proliferating activator, in melanoma cells. Besides, an inhibition of AXL and AKT was detected. All these molecular events propitiate an inhibition of autophagy, and consequently, melanoma cell death by apoptosis.
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Apoptose / GTP Fosfo-Hidrolases / Indóis / Melanoma / Proteínas de Membrana / Mutação Limite: Humans Idioma: En Revista: Tumour Biol Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Buscar no Google
Adicionar na Minha BVS
Imprimir
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PubMed Links

Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Apoptose / GTP Fosfo-Hidrolases / Indóis / Melanoma / Proteínas de Membrana / Mutação Limite: Humans Idioma: En Revista: Tumour Biol Assunto da revista: NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda