A novel kind of nitrogen heterocycle compound induces apoptosis of human chronic myelogenous leukemia K562 cells

作者：Ding, Guoyu; Liu, Feng; Yang, Ting; Jiang, Yuyang^*; Fu, Hua; Zhao, Yufen

来源：Bioorganic & Medicinal Chemistry, 2006, 14(11): 3766-3774.

DOI：10.1016/j.bmc.2006.01.050

• nitrogen heterocycle compounds
• K562 cell apoptosis
• caspase-3,8,9
• G(1) arrest

The effects of a novel kind of nitrogen heterocycle Compound, which was synthesized in our laboratory previously, on human chronic myelogenous leukemia K562 cells were investigated. The morphological changes were observed by Acridine orange (AO) staining. The screened results through DNA fragmentation and the Annexin V-FITC/PI staining assay showed that compound 8 blocked cell cycles at G(1), phase which led to apoptosis. The increase of caspase-3, 8, and 9 was detected, indicating that both of death-receptor and mitochondria-pathways were activated. Compound 8 induced a biphasic alteration in mitochondrial membrane potential of K562 cells. A dramatic elevation of Ca2 was also observed. In addition, a transient increase of ROS was also involved in the process. This Study showed that compound 8 might be a potential chemopreventive agent for chronic myelogenous leukemia. It would guide our future work to synthesize more compounds derived from compound 8, which might have better effect, and to determine the target protein. Moreover, it might also provide a background mechanism for the introduction of this new type of promising therapeutic agent.

• 出版日期2006-6-1
• 单位清华大学; 清华大学深圳研究生院