Toluquinol, a marine fungus metabolite, is a new angiossuppresor that interferes the AKT pathway
- Authors
- García-Caballero, M., Beffa, M.M., Cañedo, L., Medina, M.A., and Quesada, A.R.
- ID
- ZDB-PUB-130429-2
- Date
- 2013
- Source
- Biochemical pharmacology 85(12): 1727-40 (Journal)
- Registered Authors
- Keywords
- toluquinol, 2-methylhydroquinone, angiogenesis, cancer, marine compounds
- MeSH Terms
-
- Angiogenesis Inhibitors/isolation & purification
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Cattle
- Cell Movement/drug effects
- Cell Movement/physiology
- Cells, Cultured
- Chick Embryo
- Dose-Response Relationship, Drug
- HEK293 Cells
- HT29 Cells
- Humans
- Hydroquinones/isolation & purification
- Hydroquinones/pharmacology*
- Penicillium*/metabolism
- Proto-Oncogene Proteins c-akt/antagonists & inhibitors*
- Proto-Oncogene Proteins c-akt/metabolism
- Signal Transduction/drug effects*
- Signal Transduction/physiology
- Zebrafish
- PubMed
- 23603293 Full text @ Biochem. Pharmacol.
Toluquinol, a methylhydroquinone produced by a marine fungus, was selected in the course of a blind screening for new potential inhibitors of angiogenesis. In the present study we provide the first evidence that toluquinol is a new anti-angiogenic-compound. In a variety of experimental systems, representing the sequential events of the angiogenic process, toluquinol treatment of activated endothelial cells resulted in strong inhibitory effect. Toluquinol inhibited the growth of endothelial and tumor cells in culture in the micromolar range. Our results indicate that the observed growth inhibitory effect could be due, at least in part, to an induction of apoptosis. Toluquinol induced endothelial cell death is mediated via apoptosis after a cell cycle block and caspase activation. Capillary tube formation on Matrigel and migratory, invasive and proteolytic capabilities of endothelial cells were inhibited by addition of toluquinol at subtoxic concentrations. Inhibition of the mentioned essential steps of in vitro angiogenesis agrees with the observed inhibition of the in vivo angiogenesis, substantiated by using the chick chorioallatoic membrane assay and confirmed by the murine Matrigel plug, the zebrafish embryo neovascularization and the zefrafish caudal fin regeneration assays. Data here shown altogether indicate that toluquinol has antiangiogenic effects both in vitro and in vivo that are exerted partly by suppression of the VEGF and FGF-induced AKT activation of endothelial cells. These effects are carried out at lower concentrations to those required for other inhibitors of angiogenesis, what makes toluquinol a promising drug candidate for further evaluation in the treatment of cancer and other angiogenesis-related pathologies.