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Type: Artigo de periódico
Title: Inhibition Of Fatty Acid Synthase In Melanoma Cells Activates The Intrinsic Pathway Of Apoptosis.
Author: Zecchin, Karina G
Rossato, Franco A
Raposo, Helena F
Melo, Daniela R
Alberici, Luciane C
Oliveira, Helena C F
Castilho, Roger F
Coletta, Ricardo D
Vercesi, Aníbal E
Graner, Edgard
Abstract: Fatty acid synthase (FASN) is the metabolic enzyme responsible for the endogenous synthesis of the saturated long-chain fatty acid, palmitate. In contrast to most normal cells, FASN is overexpressed in a variety of human cancers, including cutaneous melanoma, in which its levels of expression are associated with tumor invasion and poor prognosis. We have previously shown that FASN inhibition with orlistat significantly reduces the number of spontaneous mediastinal lymph node metastases following the implantation of B16-F10 mouse melanoma cells in the peritoneal cavity of C57BL/6 mice. In this study, we investigate the biological mechanisms responsible for the FASN inhibition-induced apoptosis in B16-F10 cells. Both FASN inhibitors, cerulenin and orlistat, significantly reduced melanoma cell proliferation and activated the intrinsic pathway of apoptosis, as demonstrated by the cytochrome c release and caspase-9 and -3 activation. Further, apoptosis was preceded by an increase in both reactive oxygen species production and cytosolic calcium concentrations and independent of p53 activation and mitochondrial permeability transition. Taken together, these findings demonstrate the mitochondrial involvement in FASN inhibition-induced apoptosis in melanoma cells.
Subject: Analysis Of Variance
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Cell Survival
Cytochromes C
Dna Primers
Enzyme-linked Immunosorbent Assay
Fatty Acid Synthases
Fatty Acid Synthesis Inhibitors
Flow Cytometry
Rna Interference
Reactive Oxygen Species
Citation: Laboratory Investigation; A Journal Of Technical Methods And Pathology. v. 91, n. 2, p. 232-40, 2011-Feb.
Rights: fechado
Identifier DOI: 10.1038/labinvest.2010.157
Date Issue: 2011
Appears in Collections:Unicamp - Artigos e Outros Documentos

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