Department of Physiology, School of Medicine, National Yang-Ming University, Taipei City 11221, Taiwan, Republic of China.
J Cell Biochem. 2010 Aug 15;110(6):1495-503. doi: 10.1002/jcb.22716.
The incidence of thyroid cancer increases with age, and it is twice in women as common as in men. The undifferentiated thyroid cancer (UTC) is the most aggressive of all thyroid cancers. Unfortunately, there are almost no efficacious therapeutic modalities. It is important to develop some new effective therapies. Evodiamine is a chemical extracted from a kind of Chinese herb named Wu-Chu-Yu and has been demonstrated to be effective in preventing the growth of a variety of cancer cells. In the present study, the mechanism by which evodiamine inhibited the undifferentiated thyroid cancer cell line ARO was examined. Based on 3-(4,5-dimethylthiazol -2-yle)2,5-diphenyltetrazolium bromide (MTT) assay, cell proliferation rate was reduced dose-dependently by evodiamine, but not by rutaecarpine. According to the flow cytometric analysis, evodiamine treatment resulted in G2/M arrest and DNA fragmentation in ARO cells. The G2/M arrest was accompanied with an increase of the expression of cdc25C, cyclin B1, and cdc2-p161 protein, and it was also with a decrease of the expression of cdc2-p15. Furthermore, by using the TUNEL assay, evodiamine-induced apoptosis was observed at 48 h and extended to 72 h. Western blotting demonstrated that evodiamine treatment induced the activation of caspase-8, caspase-9, caspase-3, and the cleavage of poly ADP-ribose polymerase (PARP). These results suggested that evodiamine inhibited the growth of the ARO cells, arrested them at M phase, and induced apoptosis through caspases signaling.
甲状腺癌的发病率随年龄增长而增加，女性是男性的两倍。未分化甲状腺癌（UTC）是所有甲状腺癌中最具侵袭性的一种。不幸的是，几乎没有有效的治疗方法。因此，开发一些新的有效治疗方法非常重要。吴茱萸碱是一种从吴茱萸这种中国草药中提取的化学物质，已被证明能有效阻止多种癌细胞的生长。在本研究中，研究了吴茱萸碱抑制未分化甲状腺癌细胞系 ARO 的作用机制。基于 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定，吴茱萸碱能剂量依赖性地降低细胞增殖率，但 rutaecarpine 则不能。根据流式细胞术分析，吴茱萸碱处理导致 ARO 细胞 G2/M 期阻滞和 DNA 片段化。G2/M 期阻滞伴随着 cdc25C、细胞周期蛋白 B1 和 cdc2-p161 蛋白表达增加，同时伴随着 cdc2-p15 蛋白表达减少。此外，通过 TUNEL 测定，在 48 小时和 72 小时观察到吴茱萸碱诱导的细胞凋亡。Western blot 分析表明，吴茱萸碱处理诱导了 caspase-8、caspase-9、caspase-3 的激活和多聚 ADP-核糖聚合酶（PARP）的切割。这些结果表明，吴茱萸碱抑制了 ARO 细胞的生长，通过 caspase 信号通路将其阻滞在 M 期，并诱导细胞凋亡。
