Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Anticancer Res. 2010 Sep;30(9):3295-300.
Brucea javanica was studied to identify nuclear factor kappaB (NF-κB) inhibitors exhibiting reactive oxygen species (ROS) intracellular amplification.
Eight compounds were evaluated for selective cytotoxicity using HT-29, HeLa, and HL-60 cells, and in a NF-κB assay. Active compounds were then tested using ROS and mitochondria transmembrane potential (MTP) assays. NF-κB and nuclear factor activated T-cell (NFAT) translocation were also assessed using their respective whole cell assays.
Bruceajavanone B, bruceantin, bruceine A, (-)-hydnocarpin, and chrysoeriol exhibited cytotoxic potential and NF-κB p65 inhibition. Chrysoeriol exhibited selective cytotoxicity against leukemia cells with greater potency and also showed an ability to up-regulate NFAT transcriptional pathways through the amplification of intracellular ROS, in the presence of H2O2, to a greater degree than bruceantin and bruceine.
Chrysoeriol selectively kills leukemic cells and potentiates the amplification of ROS levels. Therefore, chrysoeriol could serve as a potential chemotherapeutic modifier for leukemia chemotherapy since leukemia cells have a higher susceptibility to elevated ROS levels.
研究鸦胆子苦醇以鉴定具有活性氧（ROS）细胞内放大作用的核因子 kappaB（NF-κB）抑制剂。
使用 HT-29、HeLa 和 HL-60 细胞以及 NF-κB 测定法评估了 8 种化合物的选择性细胞毒性。然后使用 ROS 和线粒体跨膜电位（MTP）测定法测试活性化合物。还使用各自的全细胞测定法评估了 NF-κB 和核因子激活 T 细胞（NFAT）易位。
鸦胆子苦醇 B、鸦胆子苦醇、鸦胆子碱 A、(-)-去氢鸦胆子素和芫花素表现出细胞毒性潜力和 NF-κB p65 抑制作用。芫花素对白血病细胞具有选择性细胞毒性，其效力更强，并且在 H2O2 的存在下，通过 ROS 水平的放大，比鸦胆子苦醇和鸦胆子碱更能上调 NFAT 转录途径。
芫花素选择性杀死白血病细胞并增强 ROS 水平的放大。因此，芫花素可作为白血病化疗的潜在化疗修饰剂，因为白血病细胞对升高的 ROS 水平更敏感。
