title: Ophiobolin A Induces Autophagy and Activates the Mitochondrial Pathway of Apoptosis in Human Melanoma Cells.
abstract: 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.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Rodolfo
authors.affiliation: Department of Science and Technology, University of Sannio, Benevento, Italy.
authors.forename: Mariapina
authors.initials: M
authors.lastname: Rocco
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Cattaneo
authors.affiliation: Department of Science and Technology, University of Sannio, Benevento, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Tartaglia
authors.affiliation: Proteomics & Mass Spectrometry Laboratory, ISPAAM-National Research Council, Naples, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Sassi
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Aducci
authors.affiliation: Proteomics & Mass Spectrometry Laboratory, ISPAAM-National Research Council, Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Lorenzo
authors.identifier: http://orcid.org/0000-0001-9020-0812
authors.initials: L
authors.lastname: Camoni
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Marra
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001203:Ascomycota / Q000737:chemistry; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D054830:Sesterterpenes / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D054830:Sesterterpenes; C040764:ophiobolin A