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Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors
Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from Hechtia glomerata, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from H. glomerata’s leaves and evaluated against two cancer cell lines. The CHCl(3)/MeOH (1:1) act...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922350/ https://www.ncbi.nlm.nih.gov/pubmed/33669666 http://dx.doi.org/10.3390/molecules26041096 |
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author | Stefani, Tommaso Romo-Mancillas, Antonio Carrizales-Castillo, Juan J. J. Arredondo-Espinoza, Eder Ramírez-Estrada, Karla Alcantar-Rosales, Victor M. González-Maya, Leticia Sánchez-Carranza, Jessica Nayelli Balderas-Renterías, Isaías Camacho-Corona, María del Rayo |
author_facet | Stefani, Tommaso Romo-Mancillas, Antonio Carrizales-Castillo, Juan J. J. Arredondo-Espinoza, Eder Ramírez-Estrada, Karla Alcantar-Rosales, Victor M. González-Maya, Leticia Sánchez-Carranza, Jessica Nayelli Balderas-Renterías, Isaías Camacho-Corona, María del Rayo |
author_sort | Stefani, Tommaso |
collection | PubMed |
description | Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from Hechtia glomerata, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from H. glomerata’s leaves and evaluated against two cancer cell lines. The CHCl(3)/MeOH (1:1) active extract was fractionated, and the resulting fractions were assayed against prostate adenocarcinoma PC3 and breast adenocarcinoma MCF7 cell lines. Active fraction 4 was further analyzed by high-performance liquid chromatography–quadrupole time-of-flight–mass spectrometry analysis to identify its active constituents. Among the compounds that were responsible for the cytotoxic effects of this fraction were flavonoids, phenolic acids, and aromatic compounds, of which p-coumaric acid (p-CA) and its derivatives were abundant. To understand the mechanisms that underlie p-CA cytotoxicity, a microarray assay was performed on PC3 cells that were treated or not with this compound. The results showed that mitogen-activated protein kinases (MAPKs) that regulate many cancer-related pathways were targeted by p-CA, which could be related to the reported effects of reactive oxygen species (ROS). A molecular docking study of p-CA showed that this phenolic acid targeted these protein active sites (MAPK8 and Serine/Threonine protein kinase 3) at the same binding site as their inhibitors. Thus, we hypothesize that p-CA produces ROS, directly affects the MAPK signaling pathway, and consequently causes apoptosis, among other effects. Additionally, p-CA could be used as a platform for the design of new MAPK inhibitors and re-sensitizing agents for resistant cancers. |
format | Online Article Text |
id | pubmed-7922350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79223502021-03-03 Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors Stefani, Tommaso Romo-Mancillas, Antonio Carrizales-Castillo, Juan J. J. Arredondo-Espinoza, Eder Ramírez-Estrada, Karla Alcantar-Rosales, Victor M. González-Maya, Leticia Sánchez-Carranza, Jessica Nayelli Balderas-Renterías, Isaías Camacho-Corona, María del Rayo Molecules Article Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from Hechtia glomerata, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from H. glomerata’s leaves and evaluated against two cancer cell lines. The CHCl(3)/MeOH (1:1) active extract was fractionated, and the resulting fractions were assayed against prostate adenocarcinoma PC3 and breast adenocarcinoma MCF7 cell lines. Active fraction 4 was further analyzed by high-performance liquid chromatography–quadrupole time-of-flight–mass spectrometry analysis to identify its active constituents. Among the compounds that were responsible for the cytotoxic effects of this fraction were flavonoids, phenolic acids, and aromatic compounds, of which p-coumaric acid (p-CA) and its derivatives were abundant. To understand the mechanisms that underlie p-CA cytotoxicity, a microarray assay was performed on PC3 cells that were treated or not with this compound. The results showed that mitogen-activated protein kinases (MAPKs) that regulate many cancer-related pathways were targeted by p-CA, which could be related to the reported effects of reactive oxygen species (ROS). A molecular docking study of p-CA showed that this phenolic acid targeted these protein active sites (MAPK8 and Serine/Threonine protein kinase 3) at the same binding site as their inhibitors. Thus, we hypothesize that p-CA produces ROS, directly affects the MAPK signaling pathway, and consequently causes apoptosis, among other effects. Additionally, p-CA could be used as a platform for the design of new MAPK inhibitors and re-sensitizing agents for resistant cancers. MDPI 2021-02-19 /pmc/articles/PMC7922350/ /pubmed/33669666 http://dx.doi.org/10.3390/molecules26041096 Text en © 2021 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 Stefani, Tommaso Romo-Mancillas, Antonio Carrizales-Castillo, Juan J. J. Arredondo-Espinoza, Eder Ramírez-Estrada, Karla Alcantar-Rosales, Victor M. González-Maya, Leticia Sánchez-Carranza, Jessica Nayelli Balderas-Renterías, Isaías Camacho-Corona, María del Rayo Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors |
title | Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors |
title_full | Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors |
title_fullStr | Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors |
title_full_unstemmed | Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors |
title_short | Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors |
title_sort | cytotoxic fractions from hechtia glomerata extracts and p-coumaric acid as mapk inhibitors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922350/ https://www.ncbi.nlm.nih.gov/pubmed/33669666 http://dx.doi.org/10.3390/molecules26041096 |
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