Journal
MOLECULES
Volume 25, Issue 18, Pages -Publisher
MDPI
DOI: 10.3390/molecules25184254
Keywords
AKT; PI3K signaling pathway; apoptosis; human hepatocarcinoma HepG2 cells; migration activity; proliferation; oxidative stress; ROS level; uvaol
Funding
- 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 Employment
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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 G(0)/G(1) 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.
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