Evodiamine induces caspase-dependent apoptosis and S phase arrest in human colon lovo cells
Evodiamine induces caspase-dependent apoptosis and S phase arrest in human colon lovo cells
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吴茱萸碱诱导人结肠 lovo 细胞的 caspase 依赖性细胞凋亡和 S 期阻滞
DOI：
10.1097/cad.0b013e32833d26a9
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发表时间：
2010-09-01
影响因子：
2.3
通讯作者：
Liang, Hua-Ping
中科院分区：
文献类型：
--
作者：
Zhang, Chun;Fan, Xia;Liang, Hua-Ping
乌竹玉是一种历史悠久的中草药，其主要生物活性成分之一，据报道具有抗癌活性。在本研究中，我们研究了evoldiine对人结肠lovo细胞的体外和体内抗癌作用及其可能的机制。3-（4,5 -二甲基噻唑-2-基）-2,5-二苯基溴化四氮唑实验表明，不同浓度的evoldiamine均能抑制lovo细胞的体外增殖。流式细胞术显示，60 μmol/l evolodiamine处理后，凋亡细胞和阻滞在S期的细胞百分比呈时间依赖性增加。Western blot结果显示，evolodiamine处理降低了lovo细胞中procaspase-8、procaspase-9、procaspase-3的表达，并伴有caspase-8、caspase-9、caspase-3的激活。而evoldiine对凋亡诱导因子和内切酶G的易位没有影响。此外，western blot检测还表明，evoldiine诱导的lovo细胞S期阻滞与cyclinA、cyclinA依赖性激酶2和cdc25c的蛋白表达显著降低有关。在人结肠癌异种移植瘤模型中检测了evolodiamine的体内抗肿瘤特性，结果显示evolodiamine增加了tunel阳性细胞的数量，同时下调了procaspase-8、procaspase-9和procaspase-3的表达。综上所述，evolodiamine可通过诱导caspase依赖性凋亡和S期阻滞抑制人结肠lovo细胞的体外和体内增殖。
Evodiamine, one of the major bioactive components derived from Wu-Chu-Yu, a long-standing Chinese herb, was reported to possess anticancer activity. In this study, we investigated the in-vitro and in-vivo anticancer effects of evodiamine on human colon lovo cells and their potential mechanisms. The 3-(4, 5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the in-vitro proliferation of lovo cells was inhibited by evodiamine of various concentrations. Flow cytometry showed a time-dependent increase in the percentage of apoptotic cells and cells arrested in the S phase after treatment with 60 μmol/l evodiamine. Western blot indicated that evodiamine treatment decreased the expression of procaspase-8, procaspase-9, and procaspase-3 in lovo cells, accompanied by the activation of caspase-8, caspase-9, and caspase-3. However, the translocation of apoptosis-inducing factor and endonuclease G was not affected by evodiamine. Moreover, western blot assay also suggested that evodiamine-induced S phase arrest in lovo cells was associated with a marked decrease in the protein expression of cyclinA, cyclinA-dependent kinase 2, and cdc25c. In-vivo antineoplastic characteristics of evodiamine were examined in a human colon carcinoma lovo xenograft model and results showed that evodiamine increased the number of TUNEL-positive cells accompanied by the downregulated expression of procaspase-8, procaspase-9, and procaspase-3. In conclusion, these findings indicated that evodiamine could inhibit the in-vitro and in-vivo proliferation of human colon lovo cells by inducing caspase-dependent apoptosis and S phase arrest.