The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach

Detalhes bibliográficos
Autor(a) principal: Gallo, Margareth B. C.
Data de Publicação: 2014
Outros Autores: Falso, Miranda J. S., Balem, Fernanda, Menezes, Diego Silva, Rocha, Núbia, Balachandran, Raghavan, Sturgeon, Timothy S., Pupo, Mônica T., Day, Billy W.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/7787
Resumo: University of Pittsburgh. Department of Pharmaceutical Sciences. Pittsburgh, PA, USA / Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil.
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spelling Gallo, Margareth B. C.Falso, Miranda J. S.Balem, FernandaMenezes, Diego SilvaRocha, NúbiaBalachandran, RaghavanSturgeon, Timothy S.Pupo, Mônica T.Day, Billy W.2014-06-04T12:12:27Z2014-06-04T12:12:27Z2014GALLO, M. B. et al. The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach. Planta Medica, v. 80, n. 6, p. 473-481, 2014.1439-0221https://www.arca.fiocruz.br/handle/icict/778710.1055/s-0034-1368301engGeorg Thieme VerlagThe anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approachinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversity of Pittsburgh. Department of Pharmaceutical Sciences. Pittsburgh, PA, USA / Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil.University of Pittsburgh. Department of Pharmacology & Chemical Biology. Pittsburgh, PA, USA.Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Núcleo de Biotecnologia e Bioprospecção. Salvador, BA, Brasil.Escola Bahiana de Medicina e Saúde Pública. Núcleo de Biotecnologia e Bioprospecção. Salvador, BA, Brasil.University of Pittsburgh. Department of Pharmaceutical Sciences. Pittsburgh, PA, USA.University of Pittsburgh. Center for Vaccine Research. Pittsburgh, PA, USA.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil.University of Pittsburgh. Department of Pharmaceutical Sciences. Pittsburgh, PA, USA.As a result of a program to find antitumor compounds of endophytes from medicinal Asteraceae, the steroid (22E,24R)-8,14-epoxyergosta-4,22-diene-3,6-dione (a) and the diterpene aphidicolin (b) were isolated from the filamentous fungi Papulaspora immersa and Nigrospora sphaerica, respectively, and exhibited strong cytotoxicity against HL-60 cells. A proteomic approach was used in an attempt to identify the drugs' molecular targets and their respective antiproliferative mode of action. Results suggested that the (a) growth inhibition effect occurs by G2/M cell cycle arrest via reduction of tubulin alpha and beta isomers and 14-3-3 protein gamma expression, followed by a decrease of apoptotic and inflammatory proteins, culminating in mitochondrial oxidative damage that triggered autophagy-associated cell death. Moreover, the decrease observed in the expression levels of several types of histones indicated that (a) might be disarming oncogenic pathways via direct modulation of the epigenetic machinery. Effects on cell cycle progression and induction of apoptosis caused by (b) were confirmed. In addition, protein expression profiles also revealed that aphidicolin is able to influence microtubule dynamics, modulate proteasome activator complex expression, and control the inflammatory cascade through overexpression of thymosin beta 4, RhoGDI2, and 14-3-3 proteins. Transmission electron micrographs of (b)-treated cells unveiled dose-dependent morphological characteristics of autophagy- or oncosis-like cell death.ChaetomiaceaePapulaspora immersaTrichosphaeriaceaeNigrospora sphaericaAphidicolinEpoxyergostane‑type steroidinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALGallo MBC The anti-promyelocytic....pdfGallo MBC The anti-promyelocytic....pdfapplication/pdf287729https://www.arca.fiocruz.br/bitstream/icict/7787/1/Gallo%20MBC%20The%20anti-promyelocytic....pdff3b10cfdf11f1e10e79926f3cd9f9874MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/7787/2/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD52TEXTGallo MBC The anti-promyelocytic....pdf.txtGallo MBC The anti-promyelocytic....pdf.txtExtracted texttext/plain50664https://www.arca.fiocruz.br/bitstream/icict/7787/5/Gallo%20MBC%20The%20anti-promyelocytic....pdf.txtdc442ca44e7ce71b2e6a0a1a108cfdecMD55THUMBNAILGallo MBC The anti-promyelocytic....pdf.jpgGallo MBC The anti-promyelocytic....pdf.jpgGenerated Thumbnailimage/jpeg2474https://www.arca.fiocruz.br/bitstream/icict/7787/4/Gallo%20MBC%20The%20anti-promyelocytic....pdf.jpg9385a612bc66badf812bf69dfc4d654cMD54icict/77872023-03-15 14:33:21.69oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:33:21Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach
title The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach
spellingShingle The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach
Gallo, Margareth B. C.
Chaetomiaceae
Papulaspora immersa
Trichosphaeriaceae
Nigrospora sphaerica
Aphidicolin
Epoxyergostane‑type steroid
title_short The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach
title_full The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach
title_fullStr The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach
title_full_unstemmed The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach
title_sort The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach
author Gallo, Margareth B. C.
author_facet Gallo, Margareth B. C.
Falso, Miranda J. S.
Balem, Fernanda
Menezes, Diego Silva
Rocha, Núbia
Balachandran, Raghavan
Sturgeon, Timothy S.
Pupo, Mônica T.
Day, Billy W.
author_role author
author2 Falso, Miranda J. S.
Balem, Fernanda
Menezes, Diego Silva
Rocha, Núbia
Balachandran, Raghavan
Sturgeon, Timothy S.
Pupo, Mônica T.
Day, Billy W.
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Gallo, Margareth B. C.
Falso, Miranda J. S.
Balem, Fernanda
Menezes, Diego Silva
Rocha, Núbia
Balachandran, Raghavan
Sturgeon, Timothy S.
Pupo, Mônica T.
Day, Billy W.
dc.subject.en.pt_BR.fl_str_mv Chaetomiaceae
Papulaspora immersa
Trichosphaeriaceae
Nigrospora sphaerica
Aphidicolin
Epoxyergostane‑type steroid
topic Chaetomiaceae
Papulaspora immersa
Trichosphaeriaceae
Nigrospora sphaerica
Aphidicolin
Epoxyergostane‑type steroid
description University of Pittsburgh. Department of Pharmaceutical Sciences. Pittsburgh, PA, USA / Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil.
publishDate 2014
dc.date.accessioned.fl_str_mv 2014-06-04T12:12:27Z
dc.date.available.fl_str_mv 2014-06-04T12:12:27Z
dc.date.issued.fl_str_mv 2014
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv GALLO, M. B. et al. The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach. Planta Medica, v. 80, n. 6, p. 473-481, 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/7787
dc.identifier.issn.none.fl_str_mv 1439-0221
dc.identifier.doi.pt_BR.fl_str_mv 10.1055/s-0034-1368301
identifier_str_mv GALLO, M. B. et al. The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach. Planta Medica, v. 80, n. 6, p. 473-481, 2014.
1439-0221
10.1055/s-0034-1368301
url https://www.arca.fiocruz.br/handle/icict/7787
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Georg Thieme Verlag
publisher.none.fl_str_mv Georg Thieme Verlag
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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