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Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines

Identifieur interne : 000B68 ( Main/Exploration ); précédent : 000B67; suivant : 000B69

Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines

Auteurs : Izabela N. Faria Gomes ; Renato J. Silva-Oliveira ; Viviane A. Oliveira Silva ; Marcela N. Rosa ; Patrik S. Vital ; Maria Cristina S. Barbosa ; Fábio Vieira Dos Santos ; João Gabriel M. Junqueira ; Vanessa G. P. Severino ; Bruno G. Oliveira ; Wanderson Romão ; Rui Manuel Reis [Portugal] ; Rosy Iara Maciel De Azambuja Ribeiro

Source :

RBID : PMC:6864525

Abstract

Plant-based compounds are an option to explore and perhaps overcome the limitations of current antitumor treatments. Annona coriacea Mart. is a plant with a broad spectrum of biological activities, but its antitumor activity is still unclear. The purpose of our study was to determine the effects of A. coriacea fractions on a panel of cervical cancer cell lines and a normal keratinocyte cell line. The antitumor effect was investigated in vitro by viability assays, cell cycle, apoptosis, migration, and invasion assays. Intracellular signaling was assessed by Western blot, and major compounds were identified by mass spectrometry. All fractions exhibited a cytotoxic effect on cisplatin-resistant cell lines, SiHa and HeLa. C3 and C5 were significantly more cytotoxic and selective than cisplatin in SiHa and Hela cells. However, in CaSki, a cisplatin-sensitive cell line, the compounds did not demonstrate higher cytotoxicity when compared with cisplatin. Alkaloids and acetogenins were the main compounds identified in the fractions. These fractions also markedly decreased cell proliferation with p21 increase and cell cycle arrest in G2/M. These effects were accompanied by an increase of H2AX phosphorylation levels and DNA damage index. In addition, fractions C3 and C5 promoted p62 accumulation and decrease of LC3II, as well as acid vesicle levels, indicating the inhibition of autophagic flow. These findings suggest that A. coriacea fractions may become effective antineoplastic drugs and highlight the autophagy inhibition properties of these fractions in sensitizing cervical cancer cells to treatment.


Url:
DOI: 10.3390/molecules24213963
PubMed: 31683835
PubMed Central: 6864525


Affiliations:


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Le document en format XML

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<name sortKey="Barbosa, Maria Cristina S" sort="Barbosa, Maria Cristina S" uniqKey="Barbosa M" first="Maria Cristina S." last="Barbosa">Maria Cristina S. Barbosa</name>
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<name sortKey="Dos Santos, Fabio Vieira" sort="Dos Santos, Fabio Vieira" uniqKey="Dos Santos F" first="Fábio Vieira" last="Dos Santos">Fábio Vieira Dos Santos</name>
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<name sortKey="Junqueira, Joao Gabriel M" sort="Junqueira, Joao Gabriel M" uniqKey="Junqueira J" first="João Gabriel M." last="Junqueira">João Gabriel M. Junqueira</name>
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<name sortKey="Oliveira, Bruno G" sort="Oliveira, Bruno G" uniqKey="Oliveira B" first="Bruno G" last="Oliveira">Bruno G. Oliveira</name>
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(B.G.O.);
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(B.G.O.);
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<title xml:lang="en" level="a" type="main">
<italic>Annona coriacea</italic>
Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines</title>
<author>
<name sortKey="Gomes, Izabela N Faria" sort="Gomes, Izabela N Faria" uniqKey="Gomes I" first="Izabela N. Faria" last="Gomes">Izabela N. Faria Gomes</name>
<affiliation>
<nlm:aff id="af1-molecules-24-03963">Experimental Pathology Laboratory, Federal University of São João del Rei—CCO/UFSJ, Divinópolis 35501-296, Brazil;
<email>izabela.faria.tk@hotmail.com</email>
(I.N.F.G.);
<email>patrikdasilvavital@gmail.com</email>
(P.S.V.)</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="af2-molecules-24-03963">Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, Brazil;
<email>renatokjso@gmail.com</email>
(R.J.S.-O.);
<email>vivianeaos@gmail.com</email>
(V.A.O.S.);
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<author>
<name sortKey="Silva Oliveira, Renato J" sort="Silva Oliveira, Renato J" uniqKey="Silva Oliveira R" first="Renato J." last="Silva-Oliveira">Renato J. Silva-Oliveira</name>
<affiliation>
<nlm:aff id="af2-molecules-24-03963">Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, Brazil;
<email>renatokjso@gmail.com</email>
(R.J.S.-O.);
<email>vivianeaos@gmail.com</email>
(V.A.O.S.);
<email>nr.marcela@gmail.com</email>
(M.N.R.)</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Oliveira Silva, Viviane A" sort="Oliveira Silva, Viviane A" uniqKey="Oliveira Silva V" first="Viviane A." last="Oliveira Silva">Viviane A. Oliveira Silva</name>
<affiliation>
<nlm:aff id="af2-molecules-24-03963">Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, Brazil;
<email>renatokjso@gmail.com</email>
(R.J.S.-O.);
<email>vivianeaos@gmail.com</email>
(V.A.O.S.);
<email>nr.marcela@gmail.com</email>
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</affiliation>
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<author>
<name sortKey="Rosa, Marcela N" sort="Rosa, Marcela N" uniqKey="Rosa M" first="Marcela N." last="Rosa">Marcela N. Rosa</name>
<affiliation>
<nlm:aff id="af2-molecules-24-03963">Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, Brazil;
<email>renatokjso@gmail.com</email>
(R.J.S.-O.);
<email>vivianeaos@gmail.com</email>
(V.A.O.S.);
<email>nr.marcela@gmail.com</email>
(M.N.R.)</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Vital, Patrik S" sort="Vital, Patrik S" uniqKey="Vital P" first="Patrik S." last="Vital">Patrik S. Vital</name>
<affiliation>
<nlm:aff id="af1-molecules-24-03963">Experimental Pathology Laboratory, Federal University of São João del Rei—CCO/UFSJ, Divinópolis 35501-296, Brazil;
<email>izabela.faria.tk@hotmail.com</email>
(I.N.F.G.);
<email>patrikdasilvavital@gmail.com</email>
(P.S.V.)</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Barbosa, Maria Cristina S" sort="Barbosa, Maria Cristina S" uniqKey="Barbosa M" first="Maria Cristina S." last="Barbosa">Maria Cristina S. Barbosa</name>
<affiliation>
<nlm:aff id="af3-molecules-24-03963">Laboratory of Cell Biology and Mutagenesis, Federal University of São João del Rei—CCO/UFSJ, Divinópolis 35501-296, Brazil;
<email>mariacristina@ufsj.edu.br</email>
(M.C.S.B.);
<email>fabiosantos@ufsj.edu.br</email>
(F.V.d.S.)</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Dos Santos, Fabio Vieira" sort="Dos Santos, Fabio Vieira" uniqKey="Dos Santos F" first="Fábio Vieira" last="Dos Santos">Fábio Vieira Dos Santos</name>
<affiliation>
<nlm:aff id="af3-molecules-24-03963">Laboratory of Cell Biology and Mutagenesis, Federal University of São João del Rei—CCO/UFSJ, Divinópolis 35501-296, Brazil;
<email>mariacristina@ufsj.edu.br</email>
(M.C.S.B.);
<email>fabiosantos@ufsj.edu.br</email>
(F.V.d.S.)</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Junqueira, Joao Gabriel M" sort="Junqueira, Joao Gabriel M" uniqKey="Junqueira J" first="João Gabriel M." last="Junqueira">João Gabriel M. Junqueira</name>
<affiliation>
<nlm:aff id="af4-molecules-24-03963">Special Academic Unit of Physics and Chemistry, Federal University of Goiás, Catalão 75704-020, Brazil;
<email>jgmjunqueira@gmail.com</email>
(J.G.M.J.);
<email>vanessa.pasqualotto@gmail.com</email>
(V.G.P.S.)</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Severino, Vanessa G P" sort="Severino, Vanessa G P" uniqKey="Severino V" first="Vanessa G. P." last="Severino">Vanessa G. P. Severino</name>
<affiliation>
<nlm:aff id="af4-molecules-24-03963">Special Academic Unit of Physics and Chemistry, Federal University of Goiás, Catalão 75704-020, Brazil;
<email>jgmjunqueira@gmail.com</email>
(J.G.M.J.);
<email>vanessa.pasqualotto@gmail.com</email>
(V.G.P.S.)</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Oliveira, Bruno G" sort="Oliveira, Bruno G" uniqKey="Oliveira B" first="Bruno G" last="Oliveira">Bruno G. Oliveira</name>
<affiliation>
<nlm:aff id="af5-molecules-24-03963">Petroleomic and forensic chemistry laboratory, Department of Chemistry, Federal Institute of Espirito Santo, Vitória, ES 29075-910, Brazil;
<email>brunoliveir_ra20@msn.com</email>
(B.G.O.);
<email>wandersonromao@gmail.com</email>
(W.R.)</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Romao, Wanderson" sort="Romao, Wanderson" uniqKey="Romao W" first="Wanderson" last="Romão">Wanderson Romão</name>
<affiliation>
<nlm:aff id="af5-molecules-24-03963">Petroleomic and forensic chemistry laboratory, Department of Chemistry, Federal Institute of Espirito Santo, Vitória, ES 29075-910, Brazil;
<email>brunoliveir_ra20@msn.com</email>
(B.G.O.);
<email>wandersonromao@gmail.com</email>
(W.R.)</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Reis, Rui Manuel" sort="Reis, Rui Manuel" uniqKey="Reis R" first="Rui Manuel" last="Reis">Rui Manuel Reis</name>
<affiliation>
<nlm:aff id="af2-molecules-24-03963">Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, Brazil;
<email>renatokjso@gmail.com</email>
(R.J.S.-O.);
<email>vivianeaos@gmail.com</email>
(V.A.O.S.);
<email>nr.marcela@gmail.com</email>
(M.N.R.)</nlm:aff>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="af6-molecules-24-03963">Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, 4710-057 Braga, Portugal</nlm:aff>
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</placeName>
</affiliation>
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<nlm:aff id="af7-molecules-24-03963">3ICVS/3B’s-PT Government Associate Laboratory, 4710-057 Braga, Portugal</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>3ICVS/3B’s-PT Government Associate Laboratory, 4710-057 Braga</wicri:regionArea>
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</author>
<author>
<name sortKey="Ribeiro, Rosy Iara Maciel De Azambuja" sort="Ribeiro, Rosy Iara Maciel De Azambuja" uniqKey="Ribeiro R" first="Rosy Iara Maciel De Azambuja" last="Ribeiro">Rosy Iara Maciel De Azambuja Ribeiro</name>
<affiliation>
<nlm:aff id="af1-molecules-24-03963">Experimental Pathology Laboratory, Federal University of São João del Rei—CCO/UFSJ, Divinópolis 35501-296, Brazil;
<email>izabela.faria.tk@hotmail.com</email>
(I.N.F.G.);
<email>patrikdasilvavital@gmail.com</email>
(P.S.V.)</nlm:aff>
</affiliation>
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<series>
<title level="j">Molecules</title>
<idno type="eISSN">1420-3049</idno>
<imprint>
<date when="2019">2019</date>
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<front>
<div type="abstract" xml:lang="en">
<p>Plant-based compounds are an option to explore and perhaps overcome the limitations of current antitumor treatments.
<italic>Annona coriacea</italic>
Mart. is a plant with a broad spectrum of biological activities, but its antitumor activity is still unclear. The purpose of our study was to determine the effects of
<italic>A. coriacea</italic>
fractions on a panel of cervical cancer cell lines and a normal keratinocyte cell line. The antitumor effect was investigated in vitro by viability assays, cell cycle, apoptosis, migration, and invasion assays. Intracellular signaling was assessed by Western blot, and major compounds were identified by mass spectrometry. All fractions exhibited a cytotoxic effect on cisplatin-resistant cell lines, SiHa and HeLa. C3 and C5 were significantly more cytotoxic and selective than cisplatin in SiHa and Hela cells. However, in CaSki, a cisplatin-sensitive cell line, the compounds did not demonstrate higher cytotoxicity when compared with cisplatin. Alkaloids and acetogenins were the main compounds identified in the fractions. These fractions also markedly decreased cell proliferation with p21 increase and cell cycle arrest in G2/M. These effects were accompanied by an increase of H2AX phosphorylation levels and DNA damage index. In addition, fractions C3 and C5 promoted p62 accumulation and decrease of LC3II, as well as acid vesicle levels, indicating the inhibition of autophagic flow. These findings suggest that
<italic>A. coriacea</italic>
fractions may become effective antineoplastic drugs and highlight the autophagy inhibition properties of these fractions in sensitizing cervical cancer cells to treatment.</p>
</div>
</front>
<back>
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<analytic>
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<name sortKey="Bray, F" uniqKey="Bray F">F. Bray</name>
</author>
<author>
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</author>
<author>
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</author>
<author>
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<name sortKey="De Camargos, L F" uniqKey="De Camargos L">L.F. De Camargos</name>
</author>
<author>
<name sortKey="Da Silva, I V G" uniqKey="Da Silva I">I.V.G. Da Silva</name>
</author>
<author>
<name sortKey="Varotti, F D P" uniqKey="Varotti F">F.D.P. Varotti</name>
</author>
<author>
<name sortKey="Da Silva, L M" uniqKey="Da Silva L">L.M. Da Silva</name>
</author>
<author>
<name sortKey="Moreira, L M" uniqKey="Moreira L">L.M. Moreira</name>
</author>
<author>
<name sortKey="Lyon, J P" uniqKey="Lyon J">J.P. Lyon</name>
</author>
<author>
<name sortKey="Santos, V J D S V D" uniqKey="Santos V">V.J.D.S.V.D. Santos</name>
</author>
<author>
<name sortKey="Dos Santos, F V" uniqKey="Dos Santos F">F.V. Dos Santos</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Collins, A R" uniqKey="Collins A">A.R. Collins</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
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</TEI>
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<list>
<country>
<li>Portugal</li>
</country>
<region>
<li>Région Nord (Portugal)</li>
</region>
<settlement>
<li>Braga</li>
</settlement>
<orgName>
<li>Université du Minho</li>
</orgName>
</list>
<tree>
<noCountry>
<name sortKey="Barbosa, Maria Cristina S" sort="Barbosa, Maria Cristina S" uniqKey="Barbosa M" first="Maria Cristina S." last="Barbosa">Maria Cristina S. Barbosa</name>
<name sortKey="Dos Santos, Fabio Vieira" sort="Dos Santos, Fabio Vieira" uniqKey="Dos Santos F" first="Fábio Vieira" last="Dos Santos">Fábio Vieira Dos Santos</name>
<name sortKey="Gomes, Izabela N Faria" sort="Gomes, Izabela N Faria" uniqKey="Gomes I" first="Izabela N. Faria" last="Gomes">Izabela N. Faria Gomes</name>
<name sortKey="Junqueira, Joao Gabriel M" sort="Junqueira, Joao Gabriel M" uniqKey="Junqueira J" first="João Gabriel M." last="Junqueira">João Gabriel M. Junqueira</name>
<name sortKey="Oliveira Silva, Viviane A" sort="Oliveira Silva, Viviane A" uniqKey="Oliveira Silva V" first="Viviane A." last="Oliveira Silva">Viviane A. Oliveira Silva</name>
<name sortKey="Oliveira, Bruno G" sort="Oliveira, Bruno G" uniqKey="Oliveira B" first="Bruno G" last="Oliveira">Bruno G. Oliveira</name>
<name sortKey="Ribeiro, Rosy Iara Maciel De Azambuja" sort="Ribeiro, Rosy Iara Maciel De Azambuja" uniqKey="Ribeiro R" first="Rosy Iara Maciel De Azambuja" last="Ribeiro">Rosy Iara Maciel De Azambuja Ribeiro</name>
<name sortKey="Romao, Wanderson" sort="Romao, Wanderson" uniqKey="Romao W" first="Wanderson" last="Romão">Wanderson Romão</name>
<name sortKey="Rosa, Marcela N" sort="Rosa, Marcela N" uniqKey="Rosa M" first="Marcela N." last="Rosa">Marcela N. Rosa</name>
<name sortKey="Severino, Vanessa G P" sort="Severino, Vanessa G P" uniqKey="Severino V" first="Vanessa G. P." last="Severino">Vanessa G. P. Severino</name>
<name sortKey="Silva Oliveira, Renato J" sort="Silva Oliveira, Renato J" uniqKey="Silva Oliveira R" first="Renato J." last="Silva-Oliveira">Renato J. Silva-Oliveira</name>
<name sortKey="Vital, Patrik S" sort="Vital, Patrik S" uniqKey="Vital P" first="Patrik S." last="Vital">Patrik S. Vital</name>
</noCountry>
<country name="Portugal">
<region name="Région Nord (Portugal)">
<name sortKey="Reis, Rui Manuel" sort="Reis, Rui Manuel" uniqKey="Reis R" first="Rui Manuel" last="Reis">Rui Manuel Reis</name>
</region>
<name sortKey="Reis, Rui Manuel" sort="Reis, Rui Manuel" uniqKey="Reis R" first="Rui Manuel" last="Reis">Rui Manuel Reis</name>
</country>
</tree>
</affiliations>
</record>

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