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

Gloria C. Bonel-Pérez; Amalia Pérez-Jiménez; Isabel Gris-Cárdenas; Alberto M. Parra-Pérez; José Antonio Lupiáñez; Fernando J. Reyes-Zurita; Eva Siles; René Csuk; Juan Peragón; Eva E. Rufino-Palomares

doi:10.20944/preprints202008.0112.v1

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preprints.org > chemistry > medicinal chemistry > doi: 10.20944/preprints202008.0112.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

Gloria C. Bonel-Pérez

Amalia Pérez-Jiménez

Isabel Gris-Cárdenas

Alberto M. Parra-Pérez

José Antonio Lupiáñez

Fernando J. Reyes-Zurita

Eva Siles

René Csuk

Juan Peragón

^* ,

Eva E. Rufino-Palomares

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.

DOI: 10.3390/molecules25184254

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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, Medicinal Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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