a Department of Environmental and Food Chemistry, Faculty of Pharmacy , Victor Babeş University of Medicine and Pharmacy , Timişoara , Romania.
b 'Pius Brinzeu' Timişoara County Emergency Clinical Hospital, Oncogen Institute , Timişoara , Romania.
Toxicol Mech Methods. 2018 Feb;28(2):148-156. doi: 10.1080/15376516.2017.1373881. Epub 2017 Sep 29.
Products of natural origin have become important agents in the treatment of cancer, and the active principles of natural sources could be used in combination with chemotherapeutic agents to increase their effects and to minimize their toxicity. Oleanolic (OA) and ursolic (UA) acids are intensely studied for their promising anticancer potential. The aim of this study was focused on the in vitro toxicological effects induced by UA and OA human mesenchymal stem cells and on melanoma, one of the most frequent cancers whose incidence is increasing every year. The two compounds were tested for their cytotoxic, cell cycle arrest and pro-apoptotic effects on melanoma cells (A375 and B164A5) and mesenchymal stem cells. UA exerted a cytotoxic effect in a dose-dependent manner on melanoma cells, while OA's activity has been shown to be low or moderate. Both compounds produced alterations of the cell cycle, arresting cells in the G0/G1 phase. Furthermore, UA induced significant apoptosis through the bcl-2 genes family pathway, with the decrease of the bcl-2 gene expression. The two compounds exerted selective effects on melanoma cells with no effects on human mesenchymal stem cells. The presented results reveal the anticancer potential of UA on melanoma cells, with no detectable toxicity on the mesenchymal stem cells.
天然产物已成为癌症治疗的重要药物,天然产物的活性成分可以与化疗药物联合使用,以提高疗效,降低毒性。齐墩果酸(OA)和熊果酸(UA)因其有前景的抗癌潜力而受到广泛研究。本研究旨在研究 UA 和 OA 对人骨髓间充质干细胞和黑色素瘤的体外毒理学作用,黑色素瘤是最常见的癌症之一,其发病率每年都在增加。这两种化合物在体外对黑色素瘤细胞(A375 和 B164A5)和间充质干细胞进行了细胞毒性、细胞周期停滞和促凋亡作用的测试。UA 以剂量依赖的方式对黑色素瘤细胞产生细胞毒性作用,而 OA 的活性较低或中等。两种化合物均导致细胞周期改变,使细胞停滞在 G0/G1 期。此外,UA 通过 bcl-2 基因家族途径诱导显著的细胞凋亡,降低 bcl-2 基因的表达。这两种化合物对黑色素瘤细胞具有选择性作用,对人骨髓间充质干细胞没有影响。研究结果揭示了 UA 对黑色素瘤细胞的抗癌潜力,对间充质干细胞没有检测到毒性。