Center for Pharmaceutical Sciences and Engineering, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
Faculty of basic Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China.
Molecules. 2023 Mar 21;28(6):2830. doi: 10.3390/molecules28062830.
is clinically used for the treatment of esophageal cancer, lung cancer, cancerous melanoma, asthma, pleural disorders, ascites, and pertussis, among other conditions. In this study, 12 steroids were obtained and identified from , and cynsaccatol L (), which showed the best effects in terms of inhibiting the proliferation of HepG2 cells and the immune regulation of macrophages. Furthermore, induced typical apoptotic characteristics in HepG2 cells, such as morphological changes and the caspase cascade, as well as inducing autophagy-dependent apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation. The antitumor mechanism of might be related to promoting the endocytosis and degradation of ATP1A1 protein and then down-regulating the downstream AKT and ERK signaling pathways. Furthermore, the antiproliferation effect of in co-cultivation with macrophages was investigated, which showed that promoted the apoptosis of HepG2 cells by modulating the release of inflammatory cytokines, such as TNF-α and IFN-γ; regulating the M2-subtype polarization of macrophages; promoting the phagocytosis of macrophages. In conclusion, exerted anti-proliferative effects by promoting the degradation of ATP1A1 and inhibiting the ATP1A1-AKT/ERK signaling pathway in HepG2. Furthermore, it regulated macrophage function in co-cultivation, thereby further exerting adjuvant anti-HepG2 activity.
临床上用于治疗食管癌、肺癌、恶性黑色素瘤、哮喘、胸膜疾病、腹水和百日咳等疾病。本研究从 中得到并鉴定了 12 种甾体化合物，其中 cynsaccatol L () 对 HepG2 细胞增殖的抑制和巨噬细胞的免疫调节作用最好。此外， 诱导 HepG2 细胞发生典型的凋亡特征，如形态变化和半胱天冬酶级联反应，并通过线粒体功能障碍和活性氧 (ROS) 积累诱导自噬依赖性凋亡。 的抗肿瘤机制可能与促进 ATP1A1 蛋白的内吞和降解，然后下调下游 AKT 和 ERK 信号通路有关。此外，还研究了 与巨噬细胞共培养的增殖抑制作用，结果表明 通过调节 TNF-α和 IFN-γ等炎症细胞因子的释放、调节巨噬细胞的 M2 型极化、促进巨噬细胞的吞噬作用，促进 HepG2 细胞凋亡。综上所述， 通过促进 ATP1A1 的降解和抑制 HepG2 中的 ATP1A1-AKT/ERK 信号通路，发挥抗增殖作用。此外，它调节共培养中的巨噬细胞功能，从而进一步发挥辅助抗 HepG2 活性。
