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
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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, EvaEditorial
MDPI
Materia
AKT/PI3K signaling pathway Apoptosis Human hepatocarcinoma HepG2 cells Migration activity Proliferation Oxidative stress ROS levels Uvaol
Date
2020Referencia bibliográfica
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]
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Research Plan, Action 7 of University of Jaen, Spain UJA2014/07/13; General Secretariat of Universities, Research and Technology of the Ministry of Economy, Innovation, Science and EmploymentAbstract
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.