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Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864525/ https://www.ncbi.nlm.nih.gov/pubmed/31683835 http://dx.doi.org/10.3390/molecules24213963 |
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author | Gomes, Izabela N. Faria Silva-Oliveira, Renato J. Oliveira Silva, Viviane A. Rosa, Marcela N. Vital, Patrik S. Barbosa, Maria Cristina S. dos Santos, Fábio Vieira Junqueira, João Gabriel M. Severino, Vanessa G. P. Oliveira, Bruno G Romão, Wanderson Reis, Rui Manuel Ribeiro, Rosy Iara Maciel de Azambuja |
author_facet | Gomes, Izabela N. Faria Silva-Oliveira, Renato J. Oliveira Silva, Viviane A. Rosa, Marcela N. Vital, Patrik S. Barbosa, Maria Cristina S. dos Santos, Fábio Vieira Junqueira, João Gabriel M. Severino, Vanessa G. P. Oliveira, Bruno G Romão, Wanderson Reis, Rui Manuel Ribeiro, Rosy Iara Maciel de Azambuja |
author_sort | Gomes, Izabela N. Faria |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6864525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68645252019-12-23 Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines Gomes, Izabela N. Faria Silva-Oliveira, Renato J. Oliveira Silva, Viviane A. Rosa, Marcela N. Vital, Patrik S. Barbosa, Maria Cristina S. dos Santos, Fábio Vieira Junqueira, João Gabriel M. Severino, Vanessa G. P. Oliveira, Bruno G Romão, Wanderson Reis, Rui Manuel Ribeiro, Rosy Iara Maciel de Azambuja Molecules Article 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. MDPI 2019-11-01 /pmc/articles/PMC6864525/ /pubmed/31683835 http://dx.doi.org/10.3390/molecules24213963 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gomes, Izabela N. Faria Silva-Oliveira, Renato J. Oliveira Silva, Viviane A. Rosa, Marcela N. Vital, Patrik S. Barbosa, Maria Cristina S. dos Santos, Fábio Vieira Junqueira, João Gabriel M. Severino, Vanessa G. P. Oliveira, Bruno G Romão, Wanderson Reis, Rui Manuel Ribeiro, Rosy Iara Maciel de Azambuja Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines |
title | Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines |
title_full | Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines |
title_fullStr | Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines |
title_full_unstemmed | Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines |
title_short | Annona coriacea Mart. Fractions Promote Cell Cycle Arrest and Inhibit Autophagic Flux in Human Cervical Cancer Cell Lines |
title_sort | annona coriacea mart. fractions promote cell cycle arrest and inhibit autophagic flux in human cervical cancer cell lines |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864525/ https://www.ncbi.nlm.nih.gov/pubmed/31683835 http://dx.doi.org/10.3390/molecules24213963 |
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