Cytotoxicity of portoamides in human cancer cells and analysis of the molecular mechanisms of action

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017

Autores

Ribeiro, T (Autor) Outra; Lemos, F (Autor) Outra; Preto, M (Autor) Outra; Azevedo, J (Autor) Outra; Sousa, ML (Autor) Outra; Pedro N Leao (Autor) Outra; Alexandre Campos (Autor) FCUP; Linder, S (Autor) Outra; Vitorino, R (Autor) FMUP; Vitor Vasconcelos (Autor) FCUP; Urbatzka, R (Autor) Outra

Revista

Título: PLoS ONE

Vol. 12 Nº 1

ISSN: 1932-6203

Editora: Public Library of Science

Indexação

ISI Web of Knowledge - 16 Citações

Scopus - 22 Citações

Outras Informações

ID Authenticus: P-00N-AG5

DOI: 10.1371/journal.pone.0188817

Abstract (EN): Portoamides are cyclic peptides produced and released by the cyanobacterial strain Phormidium sp. presumably to interfere with other organisms in their ecosystems (" allelopathy"). Portoamides were previously demonstrated to have an antiproliferative effect on human lung carcinoma cells, but the underlying mechanism of this activity has not been described. In the present work, the effects of portoamides on proliferation were examined in eight human cancer cell lines and two non-carcinogenic cell lines, and major differences in sensitivities were observed. To generate hypotheses with regard to molecular mechanisms of action, quantitative proteomics using 2D gel electrophoresis and MALDI-TOF/ TOF were performed on the colon carcinoma cell line HT-29. The expression of proteins involved in energy metabolism (mitochondrial respiratory chain and pentose phosphate pathway) was found to be affected. The hypothesis of altered energy metabolism was tested in further experiments. Exposure to portoamides resulted in reduced cellular ATP content, likely due to decreased mitochondrial energy production. Mitochondrial hyperpolarization and reduced mitochondrial reductive capacity was observed in treated cells. Furthermore, alterations in the expression of peroxiredoxins (PRDX4, PRDX6) and components of proteasome subunits (PSB4, PSA6) were observed in portoamide-treated cells, but these alterations were not associated with detectable increases in oxidative stress. We conclude that the cytotoxic activity of portoamides is associated with disturbance of energy metabolism, and alterations in mitochondrial structure and function.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 18