Medical Cosmetology Department of Chengdu Second People's Hospital, Chengdu 610041, China.
Aesthetic and Plastic Burn Surgery Department of West China Hospital, Sichuan University, Chengdu 610041, China.
Comput Math Methods Med. 2022 Jun 18;2022:4000733. doi: 10.1155/2022/4000733. eCollection 2022.
Growing evidence has demonstrated that high heterogeneity contributes to poor prognosis and malignancies. The existence of melanoma cancer stem-like cells (CSCs), which are a small subpopulation of melanoma cells, is responsible for tumour resistance to therapies. Recently, plant secondary metabolites have attracted attention because they are considered promising compounds that are isolated from herbs that could help to target different subpopulations of tumours. In the present study, we aimed to identify the antitumourigenic activities of the medicinal compound chelerythrine chloride (CHE) on melanoma CSCs. CHE (30-40 mol/L) induced apoptosis in A375 and A2058 CSCs. A relatively low dose of CHE (1-5 mol/L) inhibited the stemness of melanoma CSCs without inducing apoptosis. Coculture of CHE with A375 and A2058 cells also inhibited sphere formation and decreased stemness factors, including Nanog, Oct4, and Sox2. In functional characterizations, we observed that CHE treatment increased both cellular reactive oxygen species (ROS) and mitochondrial ROS, which resulted in a decrease in mitochondrial energy production and sphere formation. Abolishing CHE-induced ROS by N-acetyl-L-cysteine (NAC), a ROS scavenger, reversed the inhibitory effects of CHE on sphere formation, suggesting that CHE-induced ROS are the potential cause of the inhibition of sphere formation. In conclusion, CHE may exert its antitumour effect as an antistem cell natural compound, suggesting that selection of the antistem cell effects of natural compounds might be a promising strategy to overcome the poor prognosis of melanoma due to the presence of CSCs.
越来越多的证据表明，高度异质性导致预后不良和恶性肿瘤。黑色素瘤癌症干细胞（CSC）的存在是肿瘤对治疗产生耐药性的原因之一，CSC 是黑色素瘤细胞中的一小部分亚群。最近，植物次生代谢产物引起了人们的关注，因为它们被认为是从草药中分离出来的有前途的化合物，可以帮助针对不同的肿瘤亚群。在本研究中，我们旨在确定药用化合物氯化白屈菜红碱（CHE）对黑色素瘤 CSC 的抗肿瘤活性。CHE（30-40μmol/L）诱导 A375 和 A2058 CSC 凋亡。相对低剂量的 CHE（1-5μmol/L）抑制黑色素瘤 CSC 的干性而不诱导凋亡。 CHE 与 A375 和 A2058 细胞共培养也抑制球体形成并降低干性因子，包括 Nanog、Oct4 和 Sox2。在功能表征中，我们观察到 CHE 处理增加了细胞活性氧（ROS）和线粒体 ROS，导致线粒体能量产生减少和球体形成减少。ROS 清除剂 N-乙酰-L-半胱氨酸（NAC）消除 CHE 诱导的 ROS 逆转了 CHE 对球体形成的抑制作用，表明 CHE 诱导的 ROS 是抑制球体形成的潜在原因。总之， CHE 可能作为一种抗干细胞天然化合物发挥其抗肿瘤作用，这表明选择天然化合物的抗干细胞作用可能是克服由于 CSC 存在而导致的黑色素瘤预后不良的一种有前途的策略。
