Destabilization of mitochondrial functions as a target against breast cancer progression: Role of TPP+-linked-polyhydroxybenzoates

Cristian Sandoval-Acuña, Sebastián Fuentes-Retamal, Daniela Guzmán-Rivera, Liliana Peredo-Silva, Matías Madrid-Rojas, Solange Rebolledo, Vicente Castro-Castillo, Mario Pavani, Mabel Catalán, Juan Diego Maya, José A. Jara, Eduardo Parra, Gloria M. Calaf, Hernán Speisky, Jorge Ferreira

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

15 Citas (Scopus)

Resumen

Mitochondrion is an accepted molecular target in cancer treatment since it exhibits a higher transmembrane potential in cancer cells, making it susceptible to be targeted by lipophilic-delocalized cations of triphenylphosphonium (TPP+). Thus, we evaluated five TPP+-linked decyl polyhydroxybenzoates as potential cytotoxic agents in several human breast cancer cell lines that differ in estrogen receptor and HER2/neu expression, and in metabolic profile. Results showed that all cell lines tested were sensitive to the cytotoxic action of these compounds. The mechanism underlying the cytotoxicity would be triggered by their weak uncoupling effect on the oxidative phosphorylation system, while having a wider and safer therapeutic range than other uncouplers and a significant lowering in transmembrane potential. Noteworthy, while the TPP+-derivatives alone led to almost negligible losses of ATP, when these were added in the presence of an AMP-activated protein kinase inhibitor, the levels of ATP fell greatly. Overall, data presented suggest that decyl polyhydroxybenzoates-TPP+ and its derivatives warrant future investigation as potential anti-tumor agents.

Idioma originalInglés
Páginas (desde-hasta)2-14
Número de páginas13
PublicaciónToxicology and Applied Pharmacology
Volumen309
DOI
EstadoPublicada - 15 oct 2016
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Toxicología
  • Farmacología

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