Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Uvaol Exerts Anti-Proliferative and Pro-Apoptotic Effects on Human Hepatocarcinoma Cells by Modulating AKT/PI3K Signaling Pathway

Version 1 : Received: 4 August 2020 / Approved: 5 August 2020 / Online: 5 August 2020 (05:58:26 CEST)

A peer-reviewed article of this Preprint also exists.

Bonel-Pérez, G.C.; Pérez-Jiménez, A.; Gris-Cárdenas, I.; Parra-Pérez, A.M.; Lupiáñez, J.A.; Reyes-Zurita, F.J.; Siles, E.; Csuk, R.; Peragón, J.; Rufino-Palomares, E.E. Antiproliferative and Pro-Apoptotic Effect of Uvaol in Human Hepatocarcinoma HepG2 Cells by Affecting G0/G1 Cell Cycle Arrest, ROS Production and AKT/PI3K Signaling Pathway. Molecules 2020, 25, 4254. Bonel-Pérez, G.C.; Pérez-Jiménez, A.; Gris-Cárdenas, I.; Parra-Pérez, A.M.; Lupiáñez, J.A.; Reyes-Zurita, F.J.; Siles, E.; Csuk, R.; Peragón, J.; Rufino-Palomares, E.E. Antiproliferative and Pro-Apoptotic Effect of Uvaol in Human Hepatocarcinoma HepG2 Cells by Affecting G0/G1 Cell Cycle Arrest, ROS Production and AKT/PI3K Signaling Pathway. Molecules 2020, 25, 4254.

Abstract

Natural products have a significant role in the development of new drugs, being relevant the pentacyclic triterpenes extracted from Olea europaea. Anticancer effect of uvaol, a natural triterpene, has been scarcely studied. The aim of this study was to understand the anticancer mechanism of uvaol in HepG2 cell line. Cytotoxicity results showed a selectivity effect of uvaol with higher influence in HepG2 than WRL68 cells used as control. Uvaol presented anti-migratory capacity in HepG2, supported by the morphological changes and higher HSP-60 expression. This compound also induced arrest in G0/G1 phase and an increase in apoptosis rate. These results are supported by decreased Bcl-2 expression and down-regulation of AKT/PI3K signaling pathway. A reduction in reactive oxygen species levels in HepG2 cells was observed. Altogether, results showed anti-proliferative and pro-apoptotic effect of uvaol on hepatocellular carcinoma, constituting an interesting challenge in the development of new treatments against this type of cancer.

Keywords

AKT/PI3K signaling pathway; apoptosis; human hepatocarcinoma HepG2 cells; migration activity; proliferation; oxidative stress; ROS level; uvaol

Subject

Chemistry and Materials Science, Medicinal Chemistry

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