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

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.

Uvaol Improves the Functioning of Fibroblasts and Endothelial Cells and Accelerates the Healing of Cutaneous Wounds in Mice

“…The migration of fibroblast and endothelial cells is mediated by multiple intracellular signaling pathways, including protein kinase A (PKA) and p38-MAPK pathways [37]. Even knowing that uvaol downregulates the AKT/PI3K signaling pathway in cancer cells, such as HepG2 cells [38], knowledge remains limited about the effect of uvaol on signaling pathways of fibroblast and endothelial cells. Thus, to evaluate whether uvaol has an activating effect on these intracellular signaling pathways, we evaluated the migration of fibroblast and endothelial cells using the scratch assay in the presence of inhibitors of distinct signaling pathways.…”

Chemical Characterization, Antioxidant, Anticancer and Hypolipidimic Activities of Chamomile (Matricaria chamomilla L.)

“…Another article, declared that uvaol, natural triterpene, exerted remarkable selective anticancer effect in human hepatocarcinoma HepG2 cells [59]. An increase in apoptosis rate, down regulation of the AKT/PI3K signaling pathway and reduction in Reactive Oxygen Species (ROS) level in HepG2 cells were observed.…”

Are Ancestral Medical Practices the Future Solution to Today’s Medical Problems?

“…Among all these phytochemicals, several should be highlighted, namely, terpenoids and polyphenols, of which consequential research related to their bioactive capacities both in vitro and in vivo is being carried out [ 5 ]. Many of these compounds have properties such as anticancer, using different cancer lines, both solid and liquid [ 6 , 7 , 8 , 9 , 10 , 11 ], antiangiogenic [ 7 , 12 , 13 , 14 , 15 ], antioxidant [ 16 , 17 , 18 ], anti-inflammatory [ 19 , 20 ], cardio- and neuroprotective [ 21 , 22 ], antidiabetogenic [ 23 , 24 ], antifungal [ 25 ], antimicrobial and antiviral [ 26 , 27 ], antiparasitic [ 28 ], growth inducing [ 29 , 30 , 31 ], and enzyme inhibitory or activating [ 32 , 33 ], as well as modulators in the production of reducing equivalents whose role is essential to explain most of the processes of metabolic biosynthesis [ 34 ], of cellular and organic growth, nutrition and differentiation processes [ 35 , 36 , 37 , 38 ] as well as, of cellular detoxification processes [ 39 ] and oxygen-free radical scavenging [ 18 , 40 ].…”

“…As we have stated in this article, natural products play an important role in the development of new nutraceuticals that help to prevent and cure diseases, and in this sense, the triterpenes present in the olive tree ( Olea europaea L.) are very relevant. An example of these compounds is uvaol, and a practically innovative study of this active principle was carried out by Bonel-Pérez et al [ 15 ], in which they analyzed its anticancer and antimetastatic effects in vitro in a hepatocarcinoma cell line (HepG2). These authors show the main molecular responsible for these activities, focusing their study on the levels of the heat shock protein HSP60, on the levels of ROS, as well as those of the antiapoptotic Bcl2 and proapoptotic Bax proteins, together with a cellular arrest in the G 0 /G 1 phase and downregulation of the AKT/PI3K and MAPK signaling pathway.…”