RT Journal Article
SR Electronic
T1 Tumor-specific Cytotoxicity of 3,5-Dibenzoyl-1,4-dihydropyridines
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2033
OP 2038
VO 25
IS 3B
A1 SUFI REZA M.D. MORSHED
A1 KEN HASHIMOTO
A1 YUKIE MUROTANI
A1 MASAMI KAWASE
A1 ANAMIK SHAH
A1 KAZUE SATOH
A1 HIROTAKA KIKUCHI
A1 HIROFUMI NISHIKAWA
A1 JUN MAKI
A1 HIROSHI SAKAGAMI
YR 2005
UL http://ar.iiarjournals.org/content/25/3B/2033.abstract
AB 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