Jacaranone induces apoptosis in melanoma cells via ROS-mediated downregulation of Akt and p38 MAPK activation and displays antitumor activity in vivo.

<h4>Background</h4>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...

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Autores principales:	Mariana H Massaoka, Alisson L Matsuo, Carlos R Figueiredo, Camyla F Farias, Natália Girola, Denise C Arruda, Jorge A B Scutti, Paulete Romoff, Oriana A Favero, Marcelo J P Ferreira, João H G Lago, Luiz R Travassos
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f86b7125a8464f9fb2e07a50006a3bbb
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spelling	oai:doaj.org-article:f86b7125a8464f9fb2e07a50006a3bbb2021-11-18T07:16:08ZJacaranone induces apoptosis in melanoma cells via ROS-mediated downregulation of Akt and p38 MAPK activation and displays antitumor activity in vivo.1932-620310.1371/journal.pone.0038698https://doaj.org/article/f86b7125a8464f9fb2e07a50006a3bbb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22701695/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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 naïve mice.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>The results provide evidence for the mechanisms of action of jacaranone and emphasize the potential use of this quinone for the treatment of melanoma.Mariana H MassaokaAlisson L MatsuoCarlos R FigueiredoCamyla F FariasNatália GirolaDenise C ArrudaJorge A B ScuttiPaulete RomoffOriana A FaveroMarcelo J P FerreiraJoão H G LagoLuiz R TravassosPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e38698 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mariana H Massaoka Alisson L Matsuo Carlos R Figueiredo Camyla F Farias Natália Girola Denise C Arruda Jorge A B Scutti Paulete Romoff Oriana A Favero Marcelo J P Ferreira João H G Lago Luiz R Travassos Jacaranone induces apoptosis in melanoma cells via ROS-mediated downregulation of Akt and p38 MAPK activation and displays antitumor activity in vivo.
description	<h4>Background</h4>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 naïve mice.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>The results provide evidence for the mechanisms of action of jacaranone and emphasize the potential use of this quinone for the treatment of melanoma.
format	article
author	Mariana H Massaoka Alisson L Matsuo Carlos R Figueiredo Camyla F Farias Natália Girola Denise C Arruda Jorge A B Scutti Paulete Romoff Oriana A Favero Marcelo J P Ferreira João H G Lago Luiz R Travassos
author_facet	Mariana H Massaoka Alisson L Matsuo Carlos R Figueiredo Camyla F Farias Natália Girola Denise C Arruda Jorge A B Scutti Paulete Romoff Oriana A Favero Marcelo J P Ferreira João H G Lago Luiz R Travassos
author_sort	Mariana H Massaoka
title	Jacaranone induces apoptosis in melanoma cells via ROS-mediated downregulation of Akt and p38 MAPK activation and displays antitumor activity in vivo.
title_short	Jacaranone induces apoptosis in melanoma cells via ROS-mediated downregulation of Akt and p38 MAPK activation and displays antitumor activity in vivo.
title_full	Jacaranone induces apoptosis in melanoma cells via ROS-mediated downregulation of Akt and p38 MAPK activation and displays antitumor activity in vivo.
title_fullStr	Jacaranone induces apoptosis in melanoma cells via ROS-mediated downregulation of Akt and p38 MAPK activation and displays antitumor activity in vivo.
title_full_unstemmed	Jacaranone induces apoptosis in melanoma cells via ROS-mediated downregulation of Akt and p38 MAPK activation and displays antitumor activity in vivo.
title_sort	jacaranone induces apoptosis in melanoma cells via ros-mediated downregulation of akt and p38 mapk activation and displays antitumor activity in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f86b7125a8464f9fb2e07a50006a3bbb
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Jacaranone induces apoptosis in melanoma cells via ROS-mediated downregulation of Akt and p38 MAPK activation and displays antitumor activity in vivo.

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