Cordycepin causes p21WAF1-mediated G2/M cell-cycle arrest by regulating c-Jun N-terminal kinase activation in human bladder cancer cells
Cordycepin causes p21WAF1-mediated G2/M cell-cycle arrest by regulating c-Jun N-terminal kinase activation in human bladder cancer cells
复制标题
DOI：
10.1016/j.abb.2009.09.001
复制
发表时间：
2009-10-15
影响因子：
3.9
通讯作者：
Moon, Sung-Kwon
中科院分区：
文献类型：
--
作者：
Lee, Se-Jung;Kim, Si-Kwan;Moon, Sung-Kwon
虫草素（Cordycepin，3 '-deoxyadenosine）是蛹虫草（Cordyceps militaris）中的一种生物活性物质，具有多种药理活性。本研究揭示了虫草素在两种不同的膀胱癌细胞系5637和T-24细胞中抗肿瘤作用的新的分子机制。虫草素处理，在200 μ M（IC 50）的剂量在细胞周期进程中导致显着的和剂量依赖性的生长抑制，这主要是由于G2/M期阻滞，并导致上调p21 WAF 1的表达，独立于p53途径。此外，用虫草素处理诱导JNK（c-Jun N-末端激酶）磷酸化。使用SP 6001259（JNK特异性抑制剂）和小干扰RNA（si-JNK 1）阻断JNK功能可挽救虫草素依赖性p21 WAF 1表达，抑制细胞生长，并减少细胞周期蛋白。提示虫草素可能是治疗膀胱癌的有效药物。(C)2009 Elsevier Inc. All rights reserved.
Cordycepin (3'-deoxyadenosine), a bioactive Compound of Cordyceps militaris, has many pharmacological activities. The present Study reveals novel molecular mechanisms for the anti-tumor effects of cordycepin in two different bladder cancer cell lines, 5637 and T-24 cells. Cordycepin treatment, at a dose of 200 mu M (IC50) during cell-cycle progression resulted in significant and dose-dependent growth inhibition, which was largely due to G2/M-phase arrest, and resulted in an Up-regulation of p21WAF1 expression, independent of the p53 pathway. Moreover, treatment with cordycepin-induced phosphorylation of JNK (c-Jun N-terminal kinases). Blockade of JNK function using SP6001259 (JNK-specific inhibitor) and small interfering RNA (si-JNK1) rescued cordycepin-dependent p21WAF1 expression, inhibited cell growth, and decreased cell cycle proteins. These results suggest that cordycepin Could be an effective treatment for bladder cancer. (C) 2009 Elsevier Inc. All rights reserved.