Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain.
Department of Zoology, Faculty of Sciences, University of Granada, Avenida Fuentenueva, 1, 18071 Granada, Spain.
Molecules. 2020 Sep 16;25(18):4254. doi: 10.3390/molecules25184254.
Natural products have a significant role in the development of new drugs, being relevant the pentacyclic triterpenes extracted from . 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/G 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.
天然产物在新药开发中具有重要作用，从 中提取的五环三萜类化合物就是一个很好的例子。乌苏烷型三萜类化合物乌苏醇的抗癌作用尚未得到充分研究。本研究旨在探讨乌苏醇在 HepG2 细胞系中的抗癌机制。细胞毒性结果表明，乌苏醇对 HepG2 细胞具有选择性细胞毒性作用，其影响明显高于用作对照的 WRL68 细胞。我们的研究结果表明，乌苏醇对 HepG2 细胞具有明显的选择性抗癌活性，具有显著的抗迁移能力和 HSP-60 表达增加。此外，该三萜类化合物的给药可诱导细胞在 G1/S 期停滞，并增加细胞凋亡率。这些结果得到了抗凋亡蛋白 Bcl2 表达降低、促凋亡蛋白 Bax 表达增加以及 AKT/PI3K 信号通路下调的支持。还观察到 HepG2 细胞中活性氧（ROS）水平的降低。总之，乌苏醇对肝癌具有抗增殖和促凋亡作用，为开发针对这种癌症的新治疗方法提供了一个有趣的挑战。
