The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach.
Identifieur interne : 000E29 ( Main/Exploration ); précédent : 000E28; suivant : 000E30The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach.
Auteurs : Margareth B C. Gallo [États-Unis] ; Miranda J S. Falso [États-Unis] ; Fernanda Balem [États-Unis] ; Diego Menezes [Brésil] ; Núbia Rocha [Brésil] ; Raghavan Balachandran [États-Unis] ; Timothy S. Sturgeon [États-Unis] ; Mônica T. Pupo [Brésil] ; Billy W. Day [États-Unis]Source :
- Planta medica [ 1439-0221 ] ; 2014.
Descripteurs français
- KwdFr :
- Antinéoplasiques (pharmacologie), Antinéoplasiques (usage thérapeutique), Aphidicoline (pharmacologie), Aphidicoline (usage thérapeutique), Asteraceae (), Cellules HL-60, Champignons (), Endophytes (), Ergostérol (analogues et dérivés), Ergostérol (pharmacologie), Ergostérol (usage thérapeutique), Humains, Inflammation (), Inflammation (métabolisme), Inhibiteur bêta de la dissociation des nucléotides guanylés spécifique des protéines rho (métabolisme), Leucémie aiguë promyélocytaire (métabolisme), Leucémie aiguë promyélocytaire (traitement médicamenteux), Microtubules (), Mitochondries (), Mitochondries (métabolisme), Mort cellulaire, Points de contrôle du cycle cellulaire (), Produits biologiques (pharmacologie), Produits biologiques (usage thérapeutique), Protéines 14-3-3 (métabolisme), Protéome (métabolisme), Protéomique, Régulation de l'expression des gènes tumoraux (), Stress oxydatif, Thymosine (métabolisme), Tubuline (métabolisme).
- MESH :
- analogues et dérivés : Ergostérol.
- métabolisme : Inflammation, Inhibiteur bêta de la dissociation des nucléotides guanylés spécifique des protéines rho, Leucémie aiguë promyélocytaire, Mitochondries, Protéines 14-3-3, Protéome, Thymosine, Tubuline.
- pharmacologie : Antinéoplasiques, Aphidicoline, Ergostérol, Produits biologiques.
- traitement médicamenteux : Leucémie aiguë promyélocytaire.
- usage thérapeutique : Antinéoplasiques, Aphidicoline, Ergostérol, Produits biologiques.
- Asteraceae, Cellules HL-60, Champignons, Endophytes, Humains, Inflammation, Microtubules, Mitochondries, Mort cellulaire, Points de contrôle du cycle cellulaire, Protéomique, Régulation de l'expression des gènes tumoraux, Stress oxydatif.
English descriptors
- KwdEn :
- 14-3-3 Proteins (metabolism), Antineoplastic Agents (pharmacology), Antineoplastic Agents (therapeutic use), Aphidicolin (pharmacology), Aphidicolin (therapeutic use), Asteraceae (chemistry), Biological Products (pharmacology), Biological Products (therapeutic use), Cell Cycle Checkpoints (drug effects), Cell Death, Endophytes (chemistry), Ergosterol (analogs & derivatives), Ergosterol (pharmacology), Ergosterol (therapeutic use), Fungi (chemistry), Gene Expression Regulation, Neoplastic (drug effects), HL-60 Cells, Humans, Inflammation (metabolism), Inflammation (prevention & control), Leukemia, Promyelocytic, Acute (drug therapy), Leukemia, Promyelocytic, Acute (metabolism), Microtubules (drug effects), Mitochondria (drug effects), Mitochondria (metabolism), Oxidative Stress, Proteome (metabolism), Proteomics, Thymosin (metabolism), Tubulin (metabolism), rho Guanine Nucleotide Dissociation Inhibitor beta (metabolism).
- MESH :
- chemical , analogs & derivatives : Ergosterol.
- chemical , metabolism : 14-3-3 Proteins, Proteome, Thymosin, Tubulin, rho Guanine Nucleotide Dissociation Inhibitor beta.
- chemical , pharmacology : Antineoplastic Agents, Aphidicolin, Biological Products, Ergosterol.
- chemical , therapeutic use : Antineoplastic Agents, Aphidicolin, Biological Products, Ergosterol.
- chemistry : Asteraceae, Endophytes, Fungi.
- drug effects : Cell Cycle Checkpoints, Gene Expression Regulation, Neoplastic, Microtubules, Mitochondria.
- drug therapy : Leukemia, Promyelocytic, Acute.
- metabolism : Inflammation, Leukemia, Promyelocytic, Acute, Mitochondria.
- prevention & control : Inflammation.
- Cell Death, HL-60 Cells, Humans, Oxidative Stress, Proteomics.
Abstract
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.
DOI: 10.1055/s-0034-1368301
PubMed: 24710897
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 003157
- to stream PubMed, to step Curation: 003135
- to stream PubMed, to step Checkpoint: 003135
- to stream Ncbi, to step Merge: 001A06
- to stream Ncbi, to step Curation: 001A06
- to stream Ncbi, to step Checkpoint: 001A06
- to stream Main, to step Merge: 000E46
- to stream Main, to step Curation: 000E29
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach.</title><author><name sortKey="Gallo, Margareth B C" sort="Gallo, Margareth B C" uniqKey="Gallo M" first="Margareth B C" last="Gallo">Margareth B C. Gallo</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Falso, Miranda J S" sort="Falso, Miranda J S" uniqKey="Falso M" first="Miranda J S" last="Falso">Miranda J S. Falso</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Balem, Fernanda" sort="Balem, Fernanda" uniqKey="Balem F" first="Fernanda" last="Balem">Fernanda Balem</name><affiliation wicri:level="4"><nlm:affiliation>Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Menezes, Diego" sort="Menezes, Diego" uniqKey="Menezes D" first="Diego" last="Menezes">Diego Menezes</name><affiliation wicri:level="2"><nlm:affiliation>Mass Spectrometry Core Facility, Centro de Pesquisas Gonçalo Moniz (CPqGM) - FIOCRUZ, Salvador, BA, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Mass Spectrometry Core Facility, Centro de Pesquisas Gonçalo Moniz (CPqGM) - FIOCRUZ, Salvador, BA</wicri:regionArea><placeName><region type="state">Bahia</region></placeName></affiliation></author><author><name sortKey="Rocha, Nubia" sort="Rocha, Nubia" uniqKey="Rocha N" first="Núbia" last="Rocha">Núbia Rocha</name><affiliation wicri:level="2"><nlm:affiliation>Núcleo de Biotecnologia e Bioprospecção, Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Núcleo de Biotecnologia e Bioprospecção, Escola Bahiana de Medicina e Saúde Pública, Salvador, BA</wicri:regionArea><placeName><region type="state">Bahia</region></placeName></affiliation></author><author><name sortKey="Balachandran, Raghavan" sort="Balachandran, Raghavan" uniqKey="Balachandran R" first="Raghavan" last="Balachandran">Raghavan Balachandran</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Sturgeon, Timothy S" sort="Sturgeon, Timothy S" uniqKey="Sturgeon T" first="Timothy S" last="Sturgeon">Timothy S. Sturgeon</name><affiliation wicri:level="4"><nlm:affiliation>Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Pupo, Monica T" sort="Pupo, Monica T" uniqKey="Pupo M" first="Mônica T" last="Pupo">Mônica T. Pupo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Sciences, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - USP, Ribeirão Preto, SP, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Department of Pharmaceutical Sciences, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - USP, Ribeirão Preto, SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Day, Billy W" sort="Day, Billy W" uniqKey="Day B" first="Billy W" last="Day">Billy W. Day</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24710897</idno><idno type="pmid">24710897</idno><idno type="doi">10.1055/s-0034-1368301</idno><idno type="wicri:Area/PubMed/Corpus">003157</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">003157</idno><idno type="wicri:Area/PubMed/Curation">003135</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">003135</idno><idno type="wicri:Area/PubMed/Checkpoint">003135</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">003135</idno><idno type="wicri:Area/Ncbi/Merge">001A06</idno><idno type="wicri:Area/Ncbi/Curation">001A06</idno><idno type="wicri:Area/Ncbi/Checkpoint">001A06</idno><idno type="wicri:Area/Main/Merge">000E46</idno><idno type="wicri:Area/Main/Curation">000E29</idno><idno type="wicri:Area/Main/Exploration">000E29</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach.</title><author><name sortKey="Gallo, Margareth B C" sort="Gallo, Margareth B C" uniqKey="Gallo M" first="Margareth B C" last="Gallo">Margareth B C. Gallo</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Falso, Miranda J S" sort="Falso, Miranda J S" uniqKey="Falso M" first="Miranda J S" last="Falso">Miranda J S. Falso</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Balem, Fernanda" sort="Balem, Fernanda" uniqKey="Balem F" first="Fernanda" last="Balem">Fernanda Balem</name><affiliation wicri:level="4"><nlm:affiliation>Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Structural Biology, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Menezes, Diego" sort="Menezes, Diego" uniqKey="Menezes D" first="Diego" last="Menezes">Diego Menezes</name><affiliation wicri:level="2"><nlm:affiliation>Mass Spectrometry Core Facility, Centro de Pesquisas Gonçalo Moniz (CPqGM) - FIOCRUZ, Salvador, BA, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Mass Spectrometry Core Facility, Centro de Pesquisas Gonçalo Moniz (CPqGM) - FIOCRUZ, Salvador, BA</wicri:regionArea><placeName><region type="state">Bahia</region></placeName></affiliation></author><author><name sortKey="Rocha, Nubia" sort="Rocha, Nubia" uniqKey="Rocha N" first="Núbia" last="Rocha">Núbia Rocha</name><affiliation wicri:level="2"><nlm:affiliation>Núcleo de Biotecnologia e Bioprospecção, Escola Bahiana de Medicina e Saúde Pública, Salvador, BA, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Núcleo de Biotecnologia e Bioprospecção, Escola Bahiana de Medicina e Saúde Pública, Salvador, BA</wicri:regionArea><placeName><region type="state">Bahia</region></placeName></affiliation></author><author><name sortKey="Balachandran, Raghavan" sort="Balachandran, Raghavan" uniqKey="Balachandran R" first="Raghavan" last="Balachandran">Raghavan Balachandran</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Sturgeon, Timothy S" sort="Sturgeon, Timothy S" uniqKey="Sturgeon T" first="Timothy S" last="Sturgeon">Timothy S. Sturgeon</name><affiliation wicri:level="4"><nlm:affiliation>Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Pupo, Monica T" sort="Pupo, Monica T" uniqKey="Pupo M" first="Mônica T" last="Pupo">Mônica T. Pupo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmaceutical Sciences, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - USP, Ribeirão Preto, SP, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Department of Pharmaceutical Sciences, Faculdade de Ciências Farmacêuticas de Ribeirão Preto - USP, Ribeirão Preto, SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Day, Billy W" sort="Day, Billy W" uniqKey="Day B" first="Billy W" last="Day">Billy W. Day</name><affiliation wicri:level="4"><nlm:affiliation>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author></analytic><series><title level="j">Planta medica</title><idno type="eISSN">1439-0221</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>14-3-3 Proteins (metabolism)</term><term>Antineoplastic Agents (pharmacology)</term><term>Antineoplastic Agents (therapeutic use)</term><term>Aphidicolin (pharmacology)</term><term>Aphidicolin (therapeutic use)</term><term>Asteraceae (chemistry)</term><term>Biological Products (pharmacology)</term><term>Biological Products (therapeutic use)</term><term>Cell Cycle Checkpoints (drug effects)</term><term>Cell Death</term><term>Endophytes (chemistry)</term><term>Ergosterol (analogs & derivatives)</term><term>Ergosterol (pharmacology)</term><term>Ergosterol (therapeutic use)</term><term>Fungi (chemistry)</term><term>Gene Expression Regulation, Neoplastic (drug effects)</term><term>HL-60 Cells</term><term>Humans</term><term>Inflammation (metabolism)</term><term>Inflammation (prevention & control)</term><term>Leukemia, Promyelocytic, Acute (drug therapy)</term><term>Leukemia, Promyelocytic, Acute (metabolism)</term><term>Microtubules (drug effects)</term><term>Mitochondria (drug effects)</term><term>Mitochondria (metabolism)</term><term>Oxidative Stress</term><term>Proteome (metabolism)</term><term>Proteomics</term><term>Thymosin (metabolism)</term><term>Tubulin (metabolism)</term><term>rho Guanine Nucleotide Dissociation Inhibitor beta (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antinéoplasiques (pharmacologie)</term><term>Antinéoplasiques (usage thérapeutique)</term><term>Aphidicoline (pharmacologie)</term><term>Aphidicoline (usage thérapeutique)</term><term>Asteraceae ()</term><term>Cellules HL-60</term><term>Champignons ()</term><term>Endophytes ()</term><term>Ergostérol (analogues et dérivés)</term><term>Ergostérol (pharmacologie)</term><term>Ergostérol (usage thérapeutique)</term><term>Humains</term><term>Inflammation ()</term><term>Inflammation (métabolisme)</term><term>Inhibiteur bêta de la dissociation des nucléotides guanylés spécifique des protéines rho (métabolisme)</term><term>Leucémie aiguë promyélocytaire (métabolisme)</term><term>Leucémie aiguë promyélocytaire (traitement médicamenteux)</term><term>Microtubules ()</term><term>Mitochondries ()</term><term>Mitochondries (métabolisme)</term><term>Mort cellulaire</term><term>Points de contrôle du cycle cellulaire ()</term><term>Produits biologiques (pharmacologie)</term><term>Produits biologiques (usage thérapeutique)</term><term>Protéines 14-3-3 (métabolisme)</term><term>Protéome (métabolisme)</term><term>Protéomique</term><term>Régulation de l'expression des gènes tumoraux ()</term><term>Stress oxydatif</term><term>Thymosine (métabolisme)</term><term>Tubuline (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Ergosterol</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>14-3-3 Proteins</term><term>Proteome</term><term>Thymosin</term><term>Tubulin</term><term>rho Guanine Nucleotide Dissociation Inhibitor beta</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term><term>Aphidicolin</term><term>Biological Products</term><term>Ergosterol</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Agents</term><term>Aphidicolin</term><term>Biological Products</term><term>Ergosterol</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Ergostérol</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Asteraceae</term><term>Endophytes</term><term>Fungi</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Cycle Checkpoints</term><term>Gene Expression Regulation, Neoplastic</term><term>Microtubules</term><term>Mitochondria</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Leukemia, Promyelocytic, Acute</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Inflammation</term><term>Leukemia, Promyelocytic, Acute</term><term>Mitochondria</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Inflammation</term><term>Inhibiteur bêta de la dissociation des nucléotides guanylés spécifique des protéines rho</term><term>Leucémie aiguë promyélocytaire</term><term>Mitochondries</term><term>Protéines 14-3-3</term><term>Protéome</term><term>Thymosine</term><term>Tubuline</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antinéoplasiques</term><term>Aphidicoline</term><term>Ergostérol</term><term>Produits biologiques</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Inflammation</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Leucémie aiguë promyélocytaire</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antinéoplasiques</term><term>Aphidicoline</term><term>Ergostérol</term><term>Produits biologiques</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Death</term><term>HL-60 Cells</term><term>Humans</term><term>Oxidative Stress</term><term>Proteomics</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Asteraceae</term><term>Cellules HL-60</term><term>Champignons</term><term>Endophytes</term><term>Humains</term><term>Inflammation</term><term>Microtubules</term><term>Mitochondries</term><term>Mort cellulaire</term><term>Points de contrôle du cycle cellulaire</term><term>Protéomique</term><term>Régulation de l'expression des gènes tumoraux</term><term>Stress oxydatif</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Brésil</li><li>États-Unis</li></country><region><li>Bahia</li><li>Pennsylvanie</li><li>État de São Paulo</li></region><settlement><li>Pittsburgh</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Gallo, Margareth B C" sort="Gallo, Margareth B C" uniqKey="Gallo M" first="Margareth B C" last="Gallo">Margareth B C. Gallo</name></region><name sortKey="Balachandran, Raghavan" sort="Balachandran, Raghavan" uniqKey="Balachandran R" first="Raghavan" last="Balachandran">Raghavan Balachandran</name><name sortKey="Balem, Fernanda" sort="Balem, Fernanda" uniqKey="Balem F" first="Fernanda" last="Balem">Fernanda Balem</name><name sortKey="Day, Billy W" sort="Day, Billy W" uniqKey="Day B" first="Billy W" last="Day">Billy W. Day</name><name sortKey="Falso, Miranda J S" sort="Falso, Miranda J S" uniqKey="Falso M" first="Miranda J S" last="Falso">Miranda J S. Falso</name><name sortKey="Sturgeon, Timothy S" sort="Sturgeon, Timothy S" uniqKey="Sturgeon T" first="Timothy S" last="Sturgeon">Timothy S. Sturgeon</name></country><country name="Brésil"><region name="Bahia"><name sortKey="Menezes, Diego" sort="Menezes, Diego" uniqKey="Menezes D" first="Diego" last="Menezes">Diego Menezes</name></region><name sortKey="Pupo, Monica T" sort="Pupo, Monica T" uniqKey="Pupo M" first="Mônica T" last="Pupo">Mônica T. Pupo</name><name sortKey="Rocha, Nubia" sort="Rocha, Nubia" uniqKey="Rocha N" first="Núbia" last="Rocha">Núbia Rocha</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Amérique/explor/PittsburghV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000E29 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000E29 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Amérique
|area= PittsburghV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:24710897
|texte= The anti-promyelocytic leukemia mode of action of two endophytic secondary metabolites unveiled by a proteomic approach.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:24710897" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a PittsburghV1
| This area was generated with Dilib version V0.6.38. |  |