Cytotoxic Fractions from <i>Hechtia glomerata</i> Extracts and <i>p</i>-Coumaric Acid as MAPK Inhibitors
Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from <i>Hechtia glomerata</i>, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from <i>H. glomerata</i>’s leaves and evaluated against two cancer...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/4/1096 |
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| author | Tommaso Stefani Antonio Romo-Mancillas Juan J. J. Carrizales-Castillo Eder Arredondo-Espinoza Karla Ramírez-Estrada Victor M. Alcantar-Rosales Leticia González-Maya Jessica Nayelli Sánchez-Carranza Isaías Balderas-Renterías María del Rayo Camacho-Corona |
| author_facet | Tommaso Stefani Antonio Romo-Mancillas Juan J. J. Carrizales-Castillo Eder Arredondo-Espinoza Karla Ramírez-Estrada Victor M. Alcantar-Rosales Leticia González-Maya Jessica Nayelli Sánchez-Carranza Isaías Balderas-Renterías María del Rayo Camacho-Corona |
| author_sort | Tommaso Stefani |
| collection | DOAJ |
| description | Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from <i>Hechtia glomerata</i>, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from <i>H. glomerata</i>’s leaves and evaluated against two cancer cell lines. The CHCl<sub>3</sub>/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 <b>4</b> 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 <i>p</i>-coumaric acid (<i>p</i>-CA) and its derivatives were abundant. To understand the mechanisms that underlie <i>p</i>-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 <i>p</i>-CA, which could be related to the reported effects of reactive oxygen species (ROS). A molecular docking study of <i>p</i>-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 <i>p</i>-CA produces ROS, directly affects the MAPK signaling pathway, and consequently causes apoptosis, among other effects. Additionally, <i>p</i>-CA could be used as a platform for the design of new MAPK inhibitors and re-sensitizing agents for resistant cancers. |
| first_indexed | 2024-03-09T00:43:37Z |
| format | Article |
| id | doaj.art-4362ea3b895346a8afe1b47c6e81fe9a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T00:43:37Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4362ea3b895346a8afe1b47c6e81fe9a2023-12-11T17:38:10ZengMDPI AGMolecules1420-30492021-02-01264109610.3390/molecules26041096Cytotoxic Fractions from <i>Hechtia glomerata</i> Extracts and <i>p</i>-Coumaric Acid as MAPK InhibitorsTommaso Stefani0Antonio Romo-Mancillas1Juan J. J. Carrizales-Castillo2Eder Arredondo-Espinoza3Karla Ramírez-Estrada4Victor M. Alcantar-Rosales5Leticia González-Maya6Jessica Nayelli Sánchez-Carranza7Isaías Balderas-Renterías8María del Rayo Camacho-Corona9Facultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad S/N, Ciudad Universitaria, San Nicolás de los Garza, NL 66451, MexicoLaboratorio de Diseño Asistido por Computadora y Síntesis de Fármacos, Facultad de Quimica, Universidad Autónoma de Querétaro, Centro Universitario, Cerro de las Campanas S/N, Santiago de Querétaro, QT 76010, MexicoFacultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad S/N, Ciudad Universitaria, San Nicolás de los Garza, NL 66451, MexicoFacultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad S/N, Ciudad Universitaria, San Nicolás de los Garza, NL 66451, MexicoFacultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad S/N, Ciudad Universitaria, San Nicolás de los Garza, NL 66451, MexicoCentro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, A.C. Servicios Analíticos, Sede Noreste, Parque de Investigación e Innovación Tecnológica, Vía de la Innovación 404, Apodaca, NL 66628, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca, MO 62209, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca, MO 62209, MexicoFacultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad S/N, Ciudad Universitaria, San Nicolás de los Garza, NL 66451, MexicoFacultad de Ciencias Químicas, Universidad Autónoma de Nuevo León, Av. Universidad S/N, Ciudad Universitaria, San Nicolás de los Garza, NL 66451, MexicoPreliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from <i>Hechtia glomerata</i>, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from <i>H. glomerata</i>’s leaves and evaluated against two cancer cell lines. The CHCl<sub>3</sub>/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 <b>4</b> 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 <i>p</i>-coumaric acid (<i>p</i>-CA) and its derivatives were abundant. To understand the mechanisms that underlie <i>p</i>-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 <i>p</i>-CA, which could be related to the reported effects of reactive oxygen species (ROS). A molecular docking study of <i>p</i>-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 <i>p</i>-CA produces ROS, directly affects the MAPK signaling pathway, and consequently causes apoptosis, among other effects. Additionally, <i>p</i>-CA could be used as a platform for the design of new MAPK inhibitors and re-sensitizing agents for resistant cancers.https://www.mdpi.com/1420-3049/26/4/1096<i>Hechtia glomerata</i>cancerbioassay-guided fractionation<i>p</i>-coumaric acidkinase inhibitor |
| spellingShingle | Tommaso Stefani Antonio Romo-Mancillas Juan J. J. Carrizales-Castillo Eder Arredondo-Espinoza Karla Ramírez-Estrada Victor M. Alcantar-Rosales Leticia González-Maya Jessica Nayelli Sánchez-Carranza Isaías Balderas-Renterías María del Rayo Camacho-Corona Cytotoxic Fractions from <i>Hechtia glomerata</i> Extracts and <i>p</i>-Coumaric Acid as MAPK Inhibitors Molecules <i>Hechtia glomerata</i> cancer bioassay-guided fractionation <i>p</i>-coumaric acid kinase inhibitor |
| title | Cytotoxic Fractions from <i>Hechtia glomerata</i> Extracts and <i>p</i>-Coumaric Acid as MAPK Inhibitors |
| title_full | Cytotoxic Fractions from <i>Hechtia glomerata</i> Extracts and <i>p</i>-Coumaric Acid as MAPK Inhibitors |
| title_fullStr | Cytotoxic Fractions from <i>Hechtia glomerata</i> Extracts and <i>p</i>-Coumaric Acid as MAPK Inhibitors |
| title_full_unstemmed | Cytotoxic Fractions from <i>Hechtia glomerata</i> Extracts and <i>p</i>-Coumaric Acid as MAPK Inhibitors |
| title_short | Cytotoxic Fractions from <i>Hechtia glomerata</i> Extracts and <i>p</i>-Coumaric Acid as MAPK Inhibitors |
| title_sort | cytotoxic fractions from i hechtia glomerata i extracts and i p i coumaric acid as mapk inhibitors |
| topic | <i>Hechtia glomerata</i> cancer bioassay-guided fractionation <i>p</i>-coumaric acid kinase inhibitor |
| url | https://www.mdpi.com/1420-3049/26/4/1096 |
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