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Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos

By using a zebrafish embryo model to guide the chromatographic fractionation of antimitotic secondary metabolites, seven podophyllotoxin-type lignans were isolated from a hydroalcoholic extract obtained from the steam bark of Bursera fagaroides. The compounds were identified as podophyllotoxin (1),...

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Autores principales: Antúnez-Mojica, Mayra, Rojas-Sepúlveda, Andrés M., Mendieta-Serrano, Mario A., Gonzalez-Maya, Leticia, Marquina, Silvia, Salas-Vidal, Enrique, Alvarez, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337621/
https://www.ncbi.nlm.nih.gov/pubmed/30577489
http://dx.doi.org/10.3390/molecules24010008
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author Antúnez-Mojica, Mayra
Rojas-Sepúlveda, Andrés M.
Mendieta-Serrano, Mario A.
Gonzalez-Maya, Leticia
Marquina, Silvia
Salas-Vidal, Enrique
Alvarez, Laura
author_facet Antúnez-Mojica, Mayra
Rojas-Sepúlveda, Andrés M.
Mendieta-Serrano, Mario A.
Gonzalez-Maya, Leticia
Marquina, Silvia
Salas-Vidal, Enrique
Alvarez, Laura
author_sort Antúnez-Mojica, Mayra
collection PubMed
description By using a zebrafish embryo model to guide the chromatographic fractionation of antimitotic secondary metabolites, seven podophyllotoxin-type lignans were isolated from a hydroalcoholic extract obtained from the steam bark of Bursera fagaroides. The compounds were identified as podophyllotoxin (1), β-peltatin-A-methylether (2), 5′-desmethoxy-β-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7). The biological effects on mitosis, cell migration, and microtubule cytoskeleton remodeling of lignans 1–7 were further evaluated in zebrafish embryos by whole-mount immunolocalization of the mitotic marker phospho-histone H3 and by a tubulin antibody. We found that lignans 1, 2, 4, and 7 induced mitotic arrest, delayed cell migration, and disrupted the microtubule cytoskeleton in zebrafish embryos. Furthermore, microtubule cytoskeleton destabilization was observed also in PC3 cells, except for 7. Therefore, these results demonstrate that the cytotoxic activity of 1, 2, and 4 is mediated by their microtubule-destabilizing activity. In general, the in vivo and in vitro models here used displayed equivalent mitotic effects, which allows us to conclude that the zebrafish model can be a fast and cheap in vivo model that can be used to identify antimitotic natural products through bioassay-guided fractionation.
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spelling pubmed-63376212019-01-25 Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos Antúnez-Mojica, Mayra Rojas-Sepúlveda, Andrés M. Mendieta-Serrano, Mario A. Gonzalez-Maya, Leticia Marquina, Silvia Salas-Vidal, Enrique Alvarez, Laura Molecules Article By using a zebrafish embryo model to guide the chromatographic fractionation of antimitotic secondary metabolites, seven podophyllotoxin-type lignans were isolated from a hydroalcoholic extract obtained from the steam bark of Bursera fagaroides. The compounds were identified as podophyllotoxin (1), β-peltatin-A-methylether (2), 5′-desmethoxy-β-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7). The biological effects on mitosis, cell migration, and microtubule cytoskeleton remodeling of lignans 1–7 were further evaluated in zebrafish embryos by whole-mount immunolocalization of the mitotic marker phospho-histone H3 and by a tubulin antibody. We found that lignans 1, 2, 4, and 7 induced mitotic arrest, delayed cell migration, and disrupted the microtubule cytoskeleton in zebrafish embryos. Furthermore, microtubule cytoskeleton destabilization was observed also in PC3 cells, except for 7. Therefore, these results demonstrate that the cytotoxic activity of 1, 2, and 4 is mediated by their microtubule-destabilizing activity. In general, the in vivo and in vitro models here used displayed equivalent mitotic effects, which allows us to conclude that the zebrafish model can be a fast and cheap in vivo model that can be used to identify antimitotic natural products through bioassay-guided fractionation. MDPI 2018-12-20 /pmc/articles/PMC6337621/ /pubmed/30577489 http://dx.doi.org/10.3390/molecules24010008 Text en © 2018 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
Antúnez-Mojica, Mayra
Rojas-Sepúlveda, Andrés M.
Mendieta-Serrano, Mario A.
Gonzalez-Maya, Leticia
Marquina, Silvia
Salas-Vidal, Enrique
Alvarez, Laura
Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos
title Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos
title_full Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos
title_fullStr Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos
title_full_unstemmed Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos
title_short Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos
title_sort lignans from bursera fagaroides affect in vivo cell behavior by disturbing the tubulin cytoskeleton in zebrafish embryos
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337621/
https://www.ncbi.nlm.nih.gov/pubmed/30577489
http://dx.doi.org/10.3390/molecules24010008
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