Program

PO3-10-38

Identification of beta-escin as a promising inhibitor of in vitro and in vivo steps in neo-vascular progression

[Speaker] Ladislav Mirossay:1
[Co-author] Lenka Varinska:1, Lenka Faber:1, Martin Kello:1, Eva Petrovova:2, Ludmila Balazova:3, Gabriela Mojzisova:4, Jan Mojzis:1
1:Department of Pharmacology, University of P. J. Safarik, Faculty of Medicine, Slovakia, 2:Department of Anatomy, Histology and Physiology, University of Veterinary Medicine and Pharmacy, Kosice, Slovakia, 3:Department of Pharmacognosy and Botany, University of Veterinary Medicine and Pharmacy, Kosice, Slovakia, 4:Department of Experimental Medicine, Faculty of Medicine, Pavol Jozef Safarik University, Kosice, Slovakia

Background: Angiogenesis plays an essential role in cancer growth and metastasis. It is therefore considered as a promising target for cancer treatment. Currently used antiangiogenic agents have some limitations of their use including toxicity and high price. Nowadays it is well known that several natural compounds may modulate basic steps in angiogenesis. In the present study we evaluated the anti-angiogenic activities of beta-escin.
Methods: Human umbilical-vein endothelial cells (HUVECs) were used as an in vitro model for studying the molecular mechanism underlying the anti-angiogenic effect of beta-escin. We investigated the in vitro effects on proliferation, migration, and tube formation of HUVECs. In vivo anti-angiogenic activity was evaluated in a chick chorioallantoic membrane (CAM) angiogenesis assay. Moreover, the effect on gene expressions was determined by the RT2 ProfilerTM human angiogenesis PCR Array.
Results: It was found that beta-escin exerts inhibitory effect on the basic fibroblast growth factor (bFGF)-induced proliferation, migration and tube formation, as well as CAM angiogenesis. The inhibition of critical steps of angiogenic process observed with beta-escin could be partially explained by suppression of Akt activation in response to bFGF. Moreover, the anti-angiogenic effects of beta-escin could be mediated via inhibition of EFNB2 and FGF-1 gene expressions in endothelial cells.
Conclusions: beta-escin affects endothelial cells as a negative mediator of angiogenesis in vitro and in vivo and may therefore be considered as a promising candidate for further research elucidating its underlying mechanism of action.

Acknowledgments: This study was supported by the Slovak Research and Development Agency under the contract no. APVV-16-0446, the Grant Agency of Ministry of Education, Science, Research, and Sport of the Slovak Republic (VEGA 1/0018/16 and VEGA 1/0753/17).

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