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- Title
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.
- Authors
Bonel-Pérez, Gloria C.; Pérez-Jiménez, Amalia; Gris-Cárdenas, Isabel; Parra-Pérez, Alberto M.; Lupiáñez, José Antonio; Reyes-Zurita, Fernando J.; Siles, Eva; Csuk, René; Peragón, Juan; Rufino-Palomares, Eva E.; Barrajon-Catalan, Enrique; Weigand, Wolfgang
- Abstract
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.
- Subjects
REACTIVE oxygen species; CELL cycle; BAX protein; OLIVE; PROTEIN expression; APOPTOSIS
- Publication
Molecules, 2020, Vol 25, Issue 18, p4254
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules25184254