title: A novel kind of nitrogen heterocycle compound induces apoptosis of human chronic myelogenous leukemia K562 cells.
abstract: 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 Ca(2+) 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.
authors.affiliation: Key Laboratory of Chemical Biology, Guangdong Province, Graduate School of Shenzhen, Tsinghua University, Shenzhen 518057, PR China.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Ding
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
authors.forename: Hua
authors.initials: H
authors.lastname: Fu
authors.forename: Yufen
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D016193:G1 Phase / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D006571:Heterocyclic Compounds; D017382:Reactive Oxygen Species; D020169:Caspases; D009584:Nitrogen