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Type: Artigo
Title: Violacein Induces Death Of Ras-mutated Metastatic Melanoma By Impairing Autophagy Process
Author: Goncalves
Paola R.; Rocha-Brito
Karin J. P.; Fernandes
Maruska R. N.; Abrantes
Julia L.; Duran
Nelson; Ferreira-Halder
Carmen V.
Abstract: Treatment of metastatic melanoma still remains a challenge, since in advanced stage it is refractory to conventional treatments. Most patients with melanoma have either B-RAF or N-RAS mutations, and these oncogenes lead to activation of the RAS-RAF-MEK-ERK and AKT signal pathway, keeping active the proliferation and survival pathways in the cell. Therefore, the identification of small molecules that block metastatic cell proliferation and induce cell death is needed. Violacein, a pigment produced by Chromobacterium violaceum found in Amazon River, has been used by our group as a biotool for scrutinizing signaling pathways associated with proliferation, survival, aggressiveness, and resistance of cancer cells. In the present study, we demonstrate that violacein diminished the viability of RAS- and RAF-mutated melanoma cells (IC50 value similar to 500 nM), and more important, this effect was not abolished after treatment medium removal. Furthermore, violacein was able to reduce significantly the invasion capacity of metastatic melanoma cells in 3D culture. In the molecular context, we have shown for the first time that violacein causes a strong drop on histone deacetylase 6 expression, a proliferating activator, in melanoma cells. Besides, an inhibition of AXL and AKT was detected. All these molecular events propitiate an inhibition of autophagy, and consequently, melanoma cell death by apoptosis.
Subject: Violacein
Antitumor Activity
Skin Carcinoma
Editor: Springer
Citation: Tumor Biology. Springer, v. 37, p. 14049 - 14058, 2016.
Rights: fechado
Identifier DOI: 10.1007/s13277-016-5265-x
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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