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ZFIN ID: ZDB-PUB-181224-10
Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos
Antúnez-Mojica, M., Rojas-Sepúlveda, A.M., Mendieta-Serrano, M.A., Gonzalez-Maya, L., Marquina, S., Salas-Vidal, E., Alvarez, L.
Date: 2018
Source: Molecules   24(1): (Journal)
Registered Authors: Salas-Vidal, Enrique
Keywords: Bursera fagaroides, F-actin, cancer, cell cycle, cell migration, epiboly, lignans, microtubules, podophyllotoxin-type lignans
MeSH Terms:
  • Animals
  • Bursera/chemistry*
  • Cell Cycle/drug effects
  • Cell Movement/drug effects
  • Cytoskeleton/chemistry*
  • Lignans/chemistry*
  • Lignans/pharmacology
  • Microtubules
  • Molecular Structure
  • Tubulin/chemistry*
  • Zebrafish
PubMed: 30577489 Full text @ Molecules
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 17 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.