Dup-697, a specific COX-2 inhibitor, suppresses growth and induces apoptosis on K562 leukemia cells by cell-cycle arrest and caspase-8 activation

• Published in: Annals of hematology 2008-02, Vol.87 (2), p.121-129
• Main Authors: Peng, Hong-Ling, Zhang, Guang-Sen, Liu, Ji-Heng, Gong, Fan-Jie, Li, Rui-Juan
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Bone Marrow Cells - drug effects; Caspase 8 - drug effects; Caspase 8 - metabolism; Cell Cycle - drug effects; Cyclooxygenase 2 Inhibitors - pharmacology; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Hematology; Humans; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Medicine; Medicine & Public Health; Oncology; Original Article; Thiophenes - pharmacology
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-007-0385-4

This investigation was designed to assess the effect of DuP-697 on growth and apoptosis in a human chronic myeloid leukemia (CML) cell line (K562 cells) and primary CML cells from CML patient bone marrow. DuP-697 significantly suppressed K562 cells and primary CML cells growth and induced apoptosis in a concentration-dependent manner and the growth-inhibiting effect was independent on Philadelphia chromosome. The IC50 of DuP-697 at 36 h was 31.7 μM. It arrested G1-S phase transmit on cell cycle and its apoptosis activity was partially abrogated by pretreating K562 cells with Z-IETD-fmk, a specific inhibitor of caspase-8. This study suggested that Dup-697 suppresses growth and induces apoptosis on K562 leukemia cells by cell-cycle arrest and caspase-8 activation.