Abstract:
Leukemia is a malignant disease of the hematopoietic system, in which clonal leukemia cells accumulate and inhibit normal hematopoiesis in the bone marrow and other hematopoietic tissues as a result of uncontrolled proliferation and impaired apoptosis, among other mechanisms. In this study, the anti-leukemic effect of a compound (SGP-17-S) extracted from Chloranthus multistachys, a plant with anti-inflammatory, antibacterial and anti-tumor effects, was evaluated. The effect of SGP-17-S on the viability of leukemic cell was demonstrated by MTT assay, cell cycle, and apoptosis were assessed by flow cytometry using PI staining and Annexin V/PI double staining. Combinations of network pharmacology and cellular thermal shift assay (CETSA) with western blot were used to validate agents that act on leukemia targets. The results showed that SGP-17-S inhibited the growth of leukemia cells in a time- and dose-dependent manner. SGP-17-S blocked HEL cells in the G2 phase, induced apoptosis, decreased Bcl-2 and caspase-8 protein expression, and increased Bax and caspase-3 expression. In addition, CETSA revealed that PARP1 is an important target gene for the inhibition of HEL cell growth, and SGP-17-S exerted its action on leukemia cells by targeting PARP1. Therefore, this study might provide new solutions and ideas for the treatment of leukemia.
摘要:
白血病是造血系统的恶性疾病,其中克隆性白血病细胞由于不受控制的增殖和凋亡受损而在骨髓和其他造血组织中积累并抑制正常造血,在其他机制中。在这项研究中,从五味子中提取的化合物(SGP-17-S)的抗白血病作用,一种具有抗炎作用的植物,抗菌和抗肿瘤作用,进行了评估。MTT法证明SGP-17-S对白血病细胞活力的影响,细胞周期,通过流式细胞术使用PI染色和膜联蛋白V/PI双重染色评估细胞凋亡。网络药理学和细胞热转移测定(CETSA)与蛋白质印迹的组合用于验证作用于白血病靶标的试剂。结果表明,SGP-17-S以时间和剂量依赖的方式抑制白血病细胞的生长。SGP-17-S在G2期阻断HEL细胞,诱导细胞凋亡,Bcl-2和caspase-8蛋白表达降低,并增加Bax和caspase-3的表达。此外,CETSA揭示PARP1是抑制HEL细胞生长的重要靶基因,SGP-17-S通过靶向PARP1对白血病细胞发挥作用。因此,本研究可能为白血病的治疗提供新的解决方案和思路。