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 . The compounds were identified as podophyllotoxin ( ), β-peltatin-A-methylether ( ), 5'-desmethoxy-β-peltatin-A-methylether ( ), desmethoxy-yatein ( ), desoxypodophyllotoxin ( ), burseranin ( ), and acetyl podophyllotoxin ( ). The biological effects on mitosis, cell migration, and microtubule cytoskeleton remodeling of lignans ⁻ 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 , , and 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 . Therefore, these results demonstrate that the cytotoxic activity of , and 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.