Abstract：
Brassinin (BSN), a potent phytoalexin found in cruciferous vegetables, has been found to exhibit diverse anti-neoplastic effects on different cancers. However, the impact of BSN on chronic myelogenous leukemia (CML) cells and the possible mode of its actions have not been described earlier. We investigated the anti-cytotoxic effects of BSN on the KBM5, KCL22, K562, and LAMA84 CML cells and its underlying mechanisms of action in inducing programmed cell death. We noted that BSN could induce apoptosis, autophagy, and paraptosis in CML cells. BSN induced PARP cleavage, subG1 peak increase, and early apoptosis. The potential action of BSN on autophagy activation was confirmed by an LC3 expression and acridine orange assay. In addition, BSN induced paraptosis through increasing the reactive oxygen species (ROS) production, mitochondria damage, and endoplasmic reticulum (ER) stress. Moreover, BSN promoted the activation of the MAPK signaling pathway, and pharmacological inhibitors of this signaling pathway could alleviate all three forms of cell death induced by BSN. Our data indicated that BSN could initiate the activation of apoptosis, autophagy, and paraptosis through modulating the MAPK signaling pathway.
摘要：
油菜素（BSN），在十字花科蔬菜中发现的一种有效的植物抗毒素，已经发现对不同的癌症表现出不同的抗肿瘤作用。然而,BSN对慢性粒细胞白血病（CML）细胞的影响及其可能的作用方式之前尚未描述。我们研究了BSN对KBM5，KCL22，K562和LAMA84CML细胞的抗细胞毒性作用及其诱导程序性细胞死亡的潜在作用机制。我们注意到BSN可以诱导细胞凋亡，自噬,和CML细胞的凋亡。BSN诱导PARP裂解，subG1峰增加，和早期凋亡。通过LC3表达和吖啶橙测定证实了BSN对自噬激活的潜在作用。此外,BSN通过增加活性氧（ROS）的产生诱导凋亡，线粒体损伤，和内质网（ER）应激。此外，BSN促进MAPK信号通路的激活,该信号通路的药物抑制剂可以减轻BSN诱导的所有三种形式的细胞死亡。我们的数据表明，BSN可以启动细胞凋亡的激活，自噬,通过调节MAPK信号通路来实现凋亡。
