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
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
Affiliations
Gloria C. Bonel-Pérez
Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain
Amalia Pérez-Jiménez
Department of Zoology, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain
Isabel Gris-Cárdenas
Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain
Alberto M. Parra-Pérez
Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain
José Antonio Lupiáñez
Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain
Fernando J. Reyes-Zurita
Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain
Eva Siles
Department of Experimental Biology, University of Jaen, Campus Las Lagunillas s/n. 23071 Jaén, Spain
René Csuk
Berreich Organische Chemie, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany
Juan Peragón
Department of Experimental Biology, University of Jaen, Campus Las Lagunillas s/n. 23071 Jaén, Spain
Eva E. Rufino-Palomares
Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain
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.
