Open AccessOphiobolin A Induces Autophagy and Activates the Mitochondrial Pathway of Apoptosis in Human Melanoma Cells
Author(s) -
Carlo Rodolfo,
Mariapina Rocco,
Lucia Cattaneo,
Maria Carmela Tartaglia,
Mauro Sassi,
Patrizia Aducci,
Andrea Scaloni,
Lorenzo Camoni,
Mauro Marra
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0167672
Subject(s) - autophagy , microbiology and biotechnology , biology , apoptosis , programmed cell death , mitochondrion , viability assay , reactive oxygen species , cancer cell , fragmentation (computing) , biochemistry , cancer , genetics , ecology
Ophiobolin A, a fungal toxin from Bipolaris species known to affect different cellular processes in plants, has recently been shown to have anti-cancer activity in mammalian cells. In the present study, we investigated the anti-proliferative effect of Ophiobolin A on human melanoma A375 and CHL-1 cell lines. This cellular model was chosen because of the incidence of melanoma malignant tumor on human population and its resistance to chemical treatments. Ophyobolin A strongly reduced cell viability of melanoma cells by affecting mitochondrial functionality. The toxin induced depolarization of mitochondrial membrane potential, reactive oxygen species production and mitochondrial network fragmentation, leading to autophagy induction and ultimately resulting in cell death by activation of the mitochondrial pathway of apoptosis. Finally, a comparative proteomic investigation on A375 cells allowed to identify several Ophiobolin A down-regulated proteins, which are involved in fundamental processes for cell homeostasis and viability.