Jacaranone Induces Apoptosis in Melanoma Cells via ROS-Mediated Downregulation of Akt and p38 MAPK Activation and Displays Antitumor Activity in Vivo

Jacaranone Induces Apoptosis in Melanoma Cells via ROS-Mediated Downregulation of Akt and p38 MAPK Activation and Displays Antitumor Activity in Vivo

Author Massaoka, Mariana Hiromi Autor UNIFESP Google Scholar
Matsuo, Alisson Leonardo Autor UNIFESP Google Scholar
Figueiredo, Carlos Rogerio Autor UNIFESP Google Scholar
Farias, Camyla F. Autor UNIFESP Google Scholar
Girola, Natalia Autor UNIFESP Google Scholar
Arruda, Denise Costa Autor UNIFESP Google Scholar
Scutti, Jorge Augusto Borin Autor UNIFESP Google Scholar
Romoff, Paulete Google Scholar
Favero, Oriana A. Google Scholar
Ferreira, Marcelo J. P. Google Scholar
Lago, Joao Henrique Ghilardi Autor UNIFESP Google Scholar
Travassos, Luiz Rodolpho Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Presbiteriana Mackenzie
Abstract Background: Malignant melanoma is a deadly type of metastatic skin cancer with increased incidence over the past 30 years. Despite the advanced knowledge on the biology, immunobiology and molecular genetics of melanoma, the alternatives of treatment are limited with poor prognosis. On clinical trials, natural products and among them redox-active quinones have been tested in the attempt to control the growth of cancer cells. Recently, we isolated jacaranone from Pentacalia desiderabilis, a benzoquinone derivative that showed a broad antitumor activity and protective anti-melanoma effect in a syngeneic model. the purified substance is active at micromolar concentrations, is not hemolytic, and is not toxic in naive mice.Methodology/Principal Findings: the jacaranone antitumor activity was shown against several human cancer cell lines in vitro. Moreover, the induction of apoptosis in murine melanoma cells and jacaranone antitumor activity in vivo, in a melanoma experimental model, were also shown. Jacaranone renders antiproliferative and proapoptotic responses in tumor cells, by acting on Akt and p38 MAPK signaling pathways through generation of reactive oxygen species (ROS). the free radical scavenger N-acetyl-cysteine (NAC) was able to completely suppress cell death induced by jacaranone as it blocked Akt downregulation, p38 MAPK activation as well as upregulation of proapoptotic Bax. Notably, treatment of melanoma growing subcutaneously in mice with jacaranone significantly extended the mean survival times in a dose-dependent manner.Conclusions/Significance: the results provide evidence for the mechanisms of action of jacaranone and emphasize the potential use of this quinone for the treatment of melanoma.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2010/51423-0
Date 2012-06-06
Published in Plos One. San Francisco: Public Library Science, v. 7, n. 6, 11 p., 2012.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 11
Origin http://dx.doi.org/10.1371/journal.pone.0038698
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000305348400087
URI http://repositorio.unifesp.br/handle/11600/34988

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