TY - JOUR T1 - Tumor-specific Cytotoxicity of 3,5-Dibenzoyl-1,4-dihydropyridines JF - Anticancer Research JO - Anticancer Res SP - 2033 LP - 2038 VL - 25 IS - 3B AU - SUFI REZA M.D. MORSHED AU - KEN HASHIMOTO AU - YUKIE MUROTANI AU - MASAMI KAWASE AU - ANAMIK SHAH AU - KAZUE SATOH AU - HIROTAKA KIKUCHI AU - HIROFUMI NISHIKAWA AU - JUN MAKI AU - HIROSHI SAKAGAMI Y1 - 2005/05/01 UR - http://ar.iiarjournals.org/content/25/3B/2033.abstract N2 - In search of compounds which show tumor-specific cytotoxic activity, two 3,5-dibenzoyl-1,4-dihydropyridines (GB5, GB12) were found to show one or two orders higher cytotoxic activity against human tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG, promyelocytic leukemia HL-60) than human normal cells (gingival fibroblast HGF, pulp cells HPC, periodontal ligament fibroblasts HPLF). GB5 and GB12 weakly induced several apoptosis-associated properties, such as inter-nucleosomal DNA fragmentation, and activation of caspases -3, -8 and -9, in both HL-60 and HSC-2 cells. Western blot analysis showed that GB5 and GB12 transiently increased the expression of both anti-apoptotic protein (Bcl-2) and proapoptotic proteins (Bax and Bad) in HL-60 cells. ESR spectroscopy showed these compounds did not produce any detectable amount of radicals, nor scavenged superoxide (generated by hypoxanthine-xanthine oxidase reaction) or nitric oxide (generated by 1-hydroxy-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene), suggesting that the induction of cytotoxic action is not via a radical-mediated reaction. The present study suggests that GB5 and GB12 may induce non-apoptotic cell death in tumor cell lines. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved ER -