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Details

Autor(en) / Beteiligte
Titel
Tumor-specific Cytotoxicity of 3,5-Dibenzoyl-1,4-dihydropyridines
Ist Teil von
  • Anticancer research, 2005-05, Vol.25 (3B), p.2033-2038
Ort / Verlag
Attiki: International Institute of Anticancer Research
Erscheinungsjahr
2005
Quelle
Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
Beschreibungen/Notizen
  • 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.

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