ZFIN ID: ZDB-PUB-190828-22
Garcimultiflorone K inhibits angiogenesis through Akt/eNOS- and mTOR-dependent pathways in human endothelial progenitor cells
Yang, C.Y., Chen, C., Lin, C.Y., Chen, Y.H., Lin, C.Y., Chi, C.W., Chen, Y.J., Liu, S.C., Chang, T.K., Tang, C.H., Lai, Y.W., Tsai, H.J., Chen, J.J., Wang, S.W.
Date: 2019
Source: Phytomedicine : international journal of phytotherapy and phytopharmacology   64: 152911 (Journal)
Registered Authors: Lin, Cheng-Yung, Tsai, Huai-Jen
Keywords: Angiogenesis, Garcimultiflorone K, Signaling pathway
MeSH Terms:
  • Angiogenesis Inhibitors/chemistry
  • Angiogenesis Inhibitors/pharmacology*
  • Animals
  • Cell Differentiation/drug effects
  • Cell Proliferation/drug effects
  • Dose-Response Relationship, Drug
  • Endothelial Progenitor Cells/drug effects
  • Garcinia/chemistry*
  • Humans
  • Neovascularization, Pathologic/drug therapy*
  • Nitric Oxide Synthase Type III/metabolism
  • Phloroglucinol/chemistry
  • Phloroglucinol/pharmacology*
  • Proto-Oncogene Proteins c-akt/metabolism
  • Ribosomal Protein S6 Kinases, 70-kDa/metabolism
  • Signal Transduction/drug effects*
  • TOR Serine-Threonine Kinases/metabolism
  • Zebrafish
PubMed: 31454653 Full text @ Phytomedicine
ABSTRACT
Background Garcimultiflorone K is a novel polyprenylated polycyclic acylphloroglucinol isolated from the stems of Garcinia multiflora that exhibits promising anti-angiogenic activity in human endothelial progenitor cells (EPCs). Purpose This study sought to determine the underlying anti-angiogenic mechanisms and pharmacological properties of garcimultiflorone K. Methods We examined the anti-angiogenic effects of garcimultiflorone K and its mechanisms of action using in vitro EPC models and in vivo zebrafish embryos. Results EPCs proliferation, migration, differentiation and capillary-like tube formation were effectively and concentration-dependently inhibited by garcimultiflorone K without any signs of cytotoxicity. Our investigations revealed that garcimultiflorone K suppressed EPCs angiogenesis through Akt, mTOR, p70S6K, and eNOS signaling cascades. Notably, garcimultiflorone K dose-dependently impeded angiogenesis in zebrafish embryos. Conclusion Our data demonstrate the anti-angiogneic effects of garcimultiflorone K in both in vitro and in vivo models. Garcimultiflorone K appears to have potential in the treatment of angiogenesis-related diseases.
ADDITIONAL INFORMATION