In vitro and in vivo antiangiogenic activity of caged polyprenylated xanthones isolated from Garcinia hanburyi Hook. f

Abstract

Eleven known caged polyprenylated xanthones 1-11 were isolated from the resin of Garcinia hanburyi Hook. f., and their structures were identified by their MS, NMR and UV spectra. These xanthones showed significant cytotoxicities against four human cancer cell lines (HeLa, A549, HCT-116, and HepG-2) and strong inhibition against the proliferation of the HUVEC cell line in vitro by the MTT method. Furthermore, in an in vivo zebrafish model, xanthones 3 (morellic acid), 7 (gambogenin) and 9 (isogambogenic acid) showed comparable antiangiogenic activities with less toxicities than xanthone 1 (gambogic acid), as evaluated by death and heart rates of treated zebrafish. Xanthone 7 exhibited antiangiogenic activity with no toxicity at concentrations ranging from 8 µM to 16 µM. Meanwhile, xanthones 1, 3, 7 and 9 strongly inhibited the migration of HUVEC at a low concentration of 0.5 µM in HUVEC cell migration assay in vitro. Taken together, these findings strongly suggest that xanthone 7 might be a novel angiogenesis inhibitor.

Figure 1

The structures of caged polyprenylated xanthones 1–11 isolated from G. hanburyi.

Figure 2

Antiangiogenic effect of xanthones 1, 3, 7 and 9 in zebrafish embryos. (magnification 400×) The results shown are representative of three independent experiments.

Figure 3

Effects of xanthones on HUVEC migration in wound migration assays. (a): Control, medium alone. (b) 0.5 μM xanthone 1. (c) 0.5 μM xanthone 3. (d) 0.5 μM xanthone 7. (e) 0.5 μM xanthone 9. The results shown are representative of three independent experiments.