College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Leuk Res. 2012 Aug;36(8):1063-6. doi: 10.1016/j.leukres.2012.02.025. Epub 2012 Mar 27.
Spider venoms are a rich source of bioactive compounds with therapeutic potential. In traditional Chinese medicine, spiders and spider venoms have been used in the treatment of various ailments. In the present study, the venom of the spider Macrothele raveni potently suppressed cell growth in the myelogenous leukemia K562 cell line in a dose and time-dependent manner with an IC(50) of 5.1 μg/mL. The venom also had a low inhibitory effect on human lymphocytes with an IC(50) of approximately 36.4 μg/mL, indicating that the venom is relatively selective for leukemic cells. Venom treated K562 cells showed typical morphological indicators of apoptosis including condensation of nuclei and fragmentation of DNA. Annexin V-FITC and propidium iodide dual staining further demonstrated that the venom had potent apoptogenic activity. Venom treatment induced caspase 3 and caspase 8 activation in K562 cells and promoted PARP cleavage. The present results indicate that the venom of the spider M. raveni potently and selectively suppresses the growth of K562 cells by inducing apoptosis via caspase 3 and caspase 8 mediated signaling pathways.
蜘蛛毒液是具有治疗潜力的生物活性化合物的丰富来源。在传统的中国医学中,蜘蛛和蜘蛛毒液已被用于治疗各种疾病。在本研究中,蜘蛛 Macrothele raveni 的毒液以剂量和时间依赖的方式强烈抑制髓性白血病 K562 细胞系的细胞生长,IC50 为 5.1 μg/mL。毒液对人淋巴细胞的抑制作用也较低,IC50 约为 36.4 μg/mL,表明毒液对白血病细胞具有相对选择性。经毒液处理的 K562 细胞显示出典型的凋亡形态学指标,包括核浓缩和 DNA 片段化。Annexin V-FITC 和碘化丙啶双重染色进一步证明了毒液具有很强的促凋亡活性。毒液处理诱导 K562 细胞中 caspase 3 和 caspase 8 的激活,并促进 PARP 裂解。本研究结果表明,蜘蛛 M. raveni 的毒液通过 caspase 3 和 caspase 8 介导的信号通路诱导凋亡,强烈且选择性地抑制 K562 细胞的生长。