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 Bonel Pérez, Gloria C. B Pérez Jiménez, Amalia Gris Cárdenas, Isabel Parra Pérez, Alberto M. Lupiáñez Cara, José Antonio Reyes Zurita, Fernando Jesús Rufino Palomares, Eva AKT/PI3K signaling pathway Apoptosis Human hepatocarcinoma HepG2 cells Migration activity Proliferation Oxidative stress ROS levels Uvaol Natural products have a significant role in the development of new drugs, being relevant the pentacyclic triterpenes extracted from Olea europaea L. 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 the HepG2 cell line. Cytotoxicity results showed a selectivity effect of uvaol with higher influence in HepG2 than WRL68 cells used as control. Our results show that uvaol has a clear and selective anticancer activity in HepG2 cells supported by a significant anti-migratory capacity and a significant increase in the expression of HSP-60. Furthermore, the administration of this triterpene induces cell arrest in the G0/G1 phase, as well as an increase in the rate of cell apoptosis. These results are supported by a decrease in the expression of the anti-apoptotic protein Bcl2, an increase in the expression of the pro-apoptotic protein Bax, together with a down-regulation of the AKT/PI3K signaling pathway. A reduction in reactive oxygen species (ROS) levels in HepG2 cells was also 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. 2020-11-13T08:51:00Z 2020-11-13T08:51:00Z 2020 info:eu-repo/semantics/article Bonel-Pérez, Gloria C.; Pérez-Jiménez, Amalia; Gris-Cárdenas, Isabel; Parra-Pérez, Alberto M.; Lupiáñez, José A.; Reyes-Zurita, Fernando J.; Siles, Eva; Csuk, René; Peragón, Juan; Rufino-Palomares, Eva E. 2020. "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 25, no. 18: 4254. [doi: 10.3390/molecules25184254] http://hdl.handle.net/10481/64245 10.3390/molecules25184254 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI