Combination treatment with arsenic trioxide and irradiation enhances apoptotic effects in U937 cells through increased mitotic arrest and ROS generation
Combination treatment with arsenic trioxide and irradiation enhances apoptotic effects in U937 cells through increased mitotic arrest and ROS generation
复制标题
DOI：
10.1016/j.cbi.2008.12.015
复制
发表时间：
2009-05-15
影响因子：
5.1
通讯作者：
Wang, Ying-Jan
中科院分区：
文献类型：
--
作者：
Ho, Sheng-Yow;Chen, Wei-Chih;Wang, Ying-Jan
砷化合物在传统中药中被用作抗癌剂。电离辐射（IR）是癌症临床治疗中最有效的工具之一。诱导凋亡性细胞死亡是肿瘤细胞在放射/化学疗法影响下的重要机制，并且对这些治疗的抗性与一些具有低凋亡倾向的癌细胞系有关。不同抗肿瘤治疗方式的组合在限制通常由极高剂量的单一方案观察到的非特异性毒性方面是有利的。本研究旨在探讨放射和As 2 O3联合处理对缺乏功能性p53蛋白的人前单核细胞白血病细胞系U937细胞周期分布和凋亡的影响及其机制。我们的结果表明，联合治疗导致cdc-2的激活，这与细胞周期蛋白B的表达有关。此外，联合治疗增加了U937细胞中的凋亡性细胞死亡，这与有丝分裂停滞的诱导、细胞内活性氧（ROS）产生的增加、B细胞白血病/淋巴瘤2（Bcl-2）和B细胞白血病/淋巴瘤XL（Bcl-XL）水平的降低、线粒体膜电位的丧失和半胱天冬酶-3的活化相关。我们发现，联合辐射和As 2 O3可能是一种有效的策略，对p53缺陷型白血病细胞。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Arsenic compounds have been used as anti-cancer agents in traditional Chinese medicine. Ionizing radiation (IR) is one of the most effective tools in the clinical treatment of cancer. The induction of apoptotic cell death is a significant mechanism of tumor cells under the influence of radio-/chemotherapy, and resistance to these treatments has been linked to some cancer cell lines with a low propensity for apoptosis. A combination of different anti-tumoral treatment modalities is advantageous in limiting non-specific toxicity often observed by an exceedingly high dose of single regimen. The present study aimed at investigating the enhanced effects and mechanisms in cell cycle distribution and apoptosis of U937 cells, a human pre-monocytic leukemia cell line lacking functional p53 protein, after combination treatment with irradiation and As2O3. Our results indicated that combined treatment led to activation of cdc-2, which is related to the expression of cyclin B. In addition, combined treatment increased apoptotic cell death in U937 cells, which is correlated with the induction of mitotic arrest, the increase in intracellular reactive oxygen species (ROS) generation, the decrease in B-cell leukemia/lymphoma 2 (Bcl-2) and B-cell leukemia/lymphoma XL (Bcl-XL) levels, the loss of mitochondria membrane potential, and the activation of caspase-3. We found that combining radiation and As2O3 may be an effective strategy against p53-deficient leukemia cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.