Loperamide, an antidiarrhea drug, has antitumor activity by inducing cell apoptosis
Loperamide, an antidiarrhea drug, has antitumor activity by inducing cell apoptosis
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洛哌丁胺是一种止泻药，通过诱导细胞凋亡而具有抗肿瘤活性。
DOI：
10.1016/j.phrs.2011.11.007
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发表时间：
2012-03-01
影响因子：
9.3
通讯作者：
Wang, Yong Xiang
中科院分区：
文献类型：
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作者：
Gong, Xing Wen;Xu, Yu Hong;Wang, Yong Xiang
洛哌丁胺是一种抗腹泻药物，是一种外周阿片受体激动剂。一些其他阿片激动剂已显示促进细胞凋亡。在本研究中，我们研究了洛哌丁胺的细胞毒性和诱导肿瘤的活性。采用MTT法测定其对9株人肿瘤细胞株的细胞毒活性。流式细胞仪检测细胞凋亡。碘化丙啶（PI）染色分析亚二倍体细胞和细胞周期，Annexin V-FITC/PI染色检测早期凋亡细胞。发现洛哌丁胺可抑制所测试的肿瘤细胞系的增殖。SMMC 7721、MCF7. SPC-A1、SKOV 3-DDP、H460、HepG 2、SGC 7901、U2 OS和ACHN细胞分别为24.2 +/- 2.1 μ M、23.6 +/- 2.5 μ M、25.9 +/- 3.1 μ M、27.1 +/- 2.5 μ M、41.4 +/- 2.1 μ M、23.7 +/- 1.3 μ M，分别为35.4 ± 3.5 μ M、11.8 ± 2.8 μ M和28.5 ± 3.4 μ M。洛哌丁胺对人骨肉瘤U2 OS细胞更有效，IC 50值为11.8 +/- 2.8 μ M。同时，它还能诱导细胞凋亡，使细胞周期阻滞于G2/M期。洛哌丁胺作用6 h可观察到凋亡细胞，且多为早期凋亡细胞。在洛哌丁胺处理的细胞中，发现caspase-3的活化，即caspase-3参与洛哌丁胺诱导的细胞凋亡。这些研究结果表明，洛哌丁胺是一种潜在的抗肿瘤药物。据我们所知，这是首次报道洛哌丁胺的抗肿瘤活性。(C)2011爱思唯尔有限公司保留所有权利。
Loperamide, an antidiarrhea drug, is a peripheral opiate agonist. Some other opiate agonists have been shown to promote cell apoptosis. In this research, we studied the apoptosis-inducing and cytotoxic activities of loperamide. MIT assay was used to determine its cytotoxicity on nine established human tumor cell lines. Cell apoptosis was detected by flow cytometry. Hypodiploid cells and cell cycles were analyzed by propidium iodide (PI) staining, while early apoptotic cells were detected by annexin V-FITC/PI staining. It was found that loperamide could inhibit the proliferation of the tested tumor cell lines. The IC50 values for SMMC7721, MCF7. SPC-A1, SKOV3-DDP, H460, HepG2, SGC7901, U2OS, and ACHN cells were 24.2 +/- 2.1 mu M, 23.6 +/- 2.5 mu M, 25.9 +/- 3.1 mu M, 27.1 +/- 2.5 mu M, 41.4 +/- 2.1 mu M, 23.7 +/- 1.3 mu M, 35.4 +/- 3.5 mu M, 11.8 +/- 2.8 mu M, and 28.5 +/- 3.4 mu M, respectively. Loperamide was more effective to the human osteosarcoma U2OS cells with an IC50 value of 11.8 +/- 2.8 mu M. Meanwhile, it could induce cell apoptosis and cause G2/M-phase cell cycle arrest. The apoptotic cells could be found when treating with loperamide for 6 h and most of them belonged to early apoptosis. In loperamide-treated cells, activation of caspase-3 was found, namely that caspase-3 was involved in the loperamide-induced apoptosis. The results of these studies indicate that loperamide is a potential antitumor agent. To our knowledge, this is the first report on antitumor activity of loperamide. (C) 2011 Elsevier Ltd. All rights reserved.