Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/197963
Type: Artigo de periódico
Title: Fatty Acid Synthase Inhibition With Orlistat Promotes Apoptosis And Reduces Cell Growth And Lymph Node Metastasis In A Mouse Melanoma Model.
Author: Carvalho, Marco A
Zecchin, Karina G
Seguin, Fabiana
Bastos, Débora C
Agostini, Michelle
Rangel, Ana Lúcia C A
Veiga, Sílvio S
Raposo, Helena F
Oliveira, Helena C F
Loda, Massimo
Coletta, Ricardo D
Graner, Edgard
Abstract: Fatty acid synthase (FASN) is the enzyme responsible for the endogenous synthesis of the saturated fatty acid palmitate. In contrast to most normal cells, malignant cells depend on FASN activity for growth and survival. In fact, FASN is overexpressed in a variety of human cancers including cutaneous melanoma, in which its levels of expression are associated with a poor prognosis and depth of invasion. Here, we show that the specific inhibition of FASN activity by the antiobesity drug Orlistat or siRNA is able to significantly reduce proliferation and promote apoptosis in the mouse metastatic melanoma cell line B16-F10. These results prompted us to verify the effect of FASN inhibition on the metastatic process in a model of spontaneous melanoma metastasis, in which B16-F10 cells injected in the peritoneal cavity of C57BL/6 mice metastasize to the mediastinal lymph nodes. We observed that mice treated with Orlistat 48 hr after the inoculation of B16-F10 cells exhibited a 52% reduction in the number of mediastinal lymph node metastases, in comparison with the control animals. These results suggest that FASN activity is essential for B16-F10 melanoma cell proliferation and survival while its inactivation by Orlistat significantly reduces their metastatic spread. The chemical inhibition of FASN activity could have a potential benefit in association with the current chemotherapy for melanoma.
Subject: Animals
Apoptosis
Cell Line, Tumor
Cell Proliferation
Disease Models, Animal
Enzyme Activation
Fatty Acid Synthases
Lactones
Lymphatic Metastasis
Melanoma
Mice
Mice, Inbred C57bl
Neoplasm Transplantation
Peritoneal Neoplasms
Rights: fechado
Identifier DOI: 10.1002/ijc.23835
Address: http://www.ncbi.nlm.nih.gov/pubmed/18770866
Date Issue: 2008
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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