Plaunotol and Geranylgeraniol Induce Caspase-Mediated Apoptosis in Colon Cancer
Plaunotol and Geranylgeraniol Induce Caspase-Mediated Apoptosis in Colon Cancer
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DOI：
10.1016/j.jss.2008.04.021
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发表时间：
2009-05-15
影响因子：
2.2
通讯作者：
Takahashi, Koki
中科院分区：
文献类型：
--
作者：
Yoshikawa, Naoyuki;Yamada, Jun;Takahashi, Koki
背景资料。PLaotol是一种从泰国药用植物PLAU-NOI中提取的异戊二烯类化合物，其结构类似于香叶醇(GGOH)，后者是另一种据报道具有很强抗癌作用的异戊二烯类化合物。最近，我们报道了它对肿瘤血管生成的抑制作用和对胃癌细胞的直接作用。在这里，我们的目的是测试普鲁诺托是否对结肠癌有一定的治疗作用。材料和方法。以人结肠癌细胞株DLD1为研究对象。肿瘤细胞与普鲁诺妥醇或GGOH共同培养，用MTS法检测细胞增殖情况。Annexin V和碘化丙啶双染法或末端脱氧核苷酸法检测细胞凋亡。用流式细胞仪和蛋白质印迹分析检测caspase-3、-8和-9的活性。PLaotol和GGOH对DLD1的增殖活性有明显的抑制作用，其抑制作用依赖于诱导细胞凋亡。Plaunotol或GGOH诱导的细胞凋亡依赖于caspase-8和caspase-9通路的激活。PLaotol将是一种潜在的治疗结肠癌的抗癌药物，由于它已经在日本和泰国作为抗溃疡/抗胃炎药物用于临床，将进行临床试验以证实目前的发现。(C)2009 Elsevier Inc.保留所有权利。
Background. Plaunotol, a kind of isoprenoid extracted from a Thai medical plant, plau-noi, is structurally similar to geranylgeraniol (GGOH), another isoprenoid reported to exert strong anticancer effects. Recently, we have reported on its inhibitory effects on tumor angiogenesis and direct effects on gastric cancer cells. Here, we aimed to test whether plaunotol could have some therapeutic effect on colon cancer.Materials and methods. Human colon cancer cell line DLD1 was used. Tumor cells were cultured in the presence of plaunotol or GGOH, and their proliferation was measured by MTS assay. Apoptosis was evaluated by Annexin V and propidium iodide double-staining or terminal-deoxynucleotidyl assay. The activation of caspase-3, -8, and -9 was analyzed by flow cytometry and Western blot analysis for PRRP cleavage.Results. Plaunotol and GGOH strongly inhibited the proliferative activity of DLD1, dependent on induction of apoptosis. The induction of apoptosis by either plaunotol or GGOH was dependent on the activation of both caspase-8 and caspase-9 pathways.Conclusions. Plaunotol would be a potential anticancer agent against colon cancer, and since it is already available in Japan and Thailand for clinical use as an anti-ulcer/antigastritis agent, clinical trials will be designed to confirm the present findings. (C) 2009 Elsevier Inc. All rights reserved.