Surgery Teaching and Research Office, 602852Cangzhou Medical College, Cangzhou, China.
Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271211069034. doi: 10.1177/09603271211069034.
Taraxasterol (TX), a pentacyclic triterpene, is one of the main active constituents isolated from . A growing number of studies have reported that TX exhibits a wide range of biological activities such as anti-oxidative, anti-inflammatory, and neuro-protective effects. Recently, TX has been demonstrated to be a potential drug candidate for treatment of some types of cancers. However, the specific role of TX in melanoma remains unclear. In this study, we aimed at exploration of the effect of TX on melanoma cell viability, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) as well as the underlying mechanisms. A375 and SK-MEL-28 cells were treated with various concentrations of TX for different times. Cell viability was measured using CCK-8 assay. Cell apoptosis was determined by flow cytometry. Transwell assays were performed to measure cell migration and invasion. The expression of E-cadherin, α-catenin, N-cadherin, vimentin, p-PI3K, PI3K, p-Akt and Akt was detected using western blot. The study showed that TX induced A375 and SK-MEL-28 cell apoptosis. Furthermore, exposure to TX inhibited A375 and SK-MEL-28 cell migration and invasion. Besides, the EMT process was reversed in A375 and SK-MEL-28 cells after TX treatment. We also observed that TX reduced the protein expression of p-PI3K and p-Akt; thus, inhibiting activity of the PI3K/Akt pathway in A375 and SK-MEL-28 cells. In addition, TX treatment increased the levels of reactive oxygen species (ROS) in A375 and SK-MEL-28 cells, and treatment with the ROS scavenger NAC significantly rescued TX-induced down-regulation of p-PI3K and p-Akt in A375 and SK-MEL-28 cells. In conclusion, our study demonstrated that TX induced ROS accumulation followed by inactivation of the PI3K/Akt pathway and subsequently attenuated melanoma progression, suggesting that TX may be a potential candidate for treatment of melanoma.
蒲公英甾醇（TX）是从 中分离得到的主要活性成分之一。越来越多的研究表明，TX 具有广泛的生物学活性，如抗氧化、抗炎和神经保护作用。最近，TX 已被证明是治疗某些类型癌症的潜在药物候选物。然而，TX 在黑色素瘤中的具体作用尚不清楚。在这项研究中，我们旨在探索 TX 对黑色素瘤细胞活力、凋亡、迁移、侵袭和上皮-间充质转化（EMT）的影响及其潜在机制。用不同浓度的 TX 处理 A375 和 SK-MEL-28 细胞不同时间。使用 CCK-8 测定法测量细胞活力。通过流式细胞术测定细胞凋亡。通过 Transwell 测定法测量细胞迁移和侵袭。使用 Western blot 检测 E-钙粘蛋白、α-连环蛋白、N-钙粘蛋白、波形蛋白、p-PI3K、PI3K、p-Akt 和 Akt 的表达。研究表明，TX 诱导 A375 和 SK-MEL-28 细胞凋亡。此外，暴露于 TX 抑制了 A375 和 SK-MEL-28 细胞的迁移和侵袭。此外，TX 处理后 A375 和 SK-MEL-28 细胞中的 EMT 过程被逆转。我们还观察到 TX 降低了 p-PI3K 和 p-Akt 的蛋白表达；从而抑制了 A375 和 SK-MEL-28 细胞中 PI3K/Akt 通路的活性。此外，TX 处理增加了 A375 和 SK-MEL-28 细胞中活性氧（ROS）的水平，并且 ROS 清除剂 NAC 的处理显著挽救了 TX 诱导的 A375 和 SK-MEL-28 细胞中 p-PI3K 和 p-Akt 的下调。总之，我们的研究表明，TX 诱导 ROS 积累，随后使 PI3K/Akt 通路失活，从而减弱黑色素瘤的进展，提示 TX 可能是治疗黑色素瘤的潜在候选药物。
