Anti-cancer effect and apoptosis induction of cordycepin through DR3 pathway in the human colonic cancer cell HT-29
Anti-cancer effect and apoptosis induction of cordycepin through DR3 pathway in the human colonic cancer cell HT-29
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DOI：
10.1016/j.fct.2013.07.068
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发表时间：
2013-10-01
影响因子：
4.3
通讯作者：
Lim, Beong Ou
中科院分区：
文献类型：
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作者：
Lee, Seung Yuan;Debnath, Trishna;Lim, Beong Ou
虫草素具有抗肿瘤、抗炎、抗血管生成等药理作用。然而，虫草素通过DR 3途径诱导人结肠癌细胞凋亡还没有研究。本实验研究了虫草素的抗增殖作用。虫草素以剂量和时间依赖性方式显著抑制细胞活力。虫草素在100 μ M的浓度下增加HT-29细胞的亚G1和G2/M期阻滞，而在200 μ M和400 μ M的浓度下增加G1期阻滞。Hoechst和Annexin V-FITC染色显示虫草素以剂量依赖方式诱导HT-29细胞凋亡。与对照细胞相比，虫草素处理的细胞中细胞内ROS水平更高。用抗体芯片检测凋亡相关蛋白。用虫草素处理18小时，p53和Bax表达增加。DR 3、caspase-8、caspase-1、裂解的caspase-3和裂解的PARP表达增加。这些发现表明虫草素通过DR 3途径诱导人结肠癌HT-29细胞凋亡。这些结果表明，虫草素应进一步评估作为一种治疗剂在人类结肠癌。(C)2013爱思唯尔有限公司保留所有权利。
Cordycepin is known to have many pharmacological effects such as anti-tumorigenic, anti-inflammatory and anti-angiogenic activity. However, cordycepin induced apoptosis through the DR3 pathway in human colon cancer cells has not been studied. The effect of cordycepin on anti-proliferation was investigated in this study. Cordycepin significantly inhibited cell viability in a dose and time-dependent manner. Cordycepin increased sub G1 and G2/M phase arrest on HT-29 cells at the concentration of 100 mu M, whereas cordycepin at 200 mu M and 400 mu M increased G1 phase arrest. Cordycepin induced apoptosis in HT-29 cells in a dose-dependent manner as detected by Hoechst and Annexin V-FITC staining. Intracellular ROS levels were higher in cordycepin treated cells as compared to control cells. The protein related to apoptosis was determined by antibody array. p53 and Bax expression increased treatment with cordycepin for 18 h. DR3, caspase-8, caspase-1, cleaved caspase-3 and cleaved PARP expression increased. These finding suggest that the cordycepin induces apoptosis through the DR3 pathway in human colon cancer HT-29. These findings suggest that cordycepin should be evaluated further as a therapeutic agent in human colon cancer. (C) 2013 Elsevier Ltd. All rights reserved.