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Research ArticleExperimental Studies

Tumor-specific Cytotoxicity of 3,5-Dibenzoyl-1,4-dihydropyridines

SUFI REZA M.D. MORSHED, KEN HASHIMOTO, YUKIE MUROTANI, MASAMI KAWASE, ANAMIK SHAH, KAZUE SATOH, HIROTAKA KIKUCHI, HIROFUMI NISHIKAWA, JUN MAKI and HIROSHI SAKAGAMI
Anticancer Research May 2005, 25 (3B) 2033-2038;
SUFI REZA M.D. MORSHED
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KEN HASHIMOTO
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YUKIE MUROTANI
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MASAMI KAWASE
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ANAMIK SHAH
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KAZUE SATOH
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HIROTAKA KIKUCHI
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HIROFUMI NISHIKAWA
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JUN MAKI
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HIROSHI SAKAGAMI
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  • For correspondence: sakagami@dent.meikai.ac.jp
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Abstract

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.

  • 3,5-Dibenzoyl-1,4-dihydropyridines
  • tumor-specificity
  • DNA fragmentation
  • caspase
  • Bcl-2
  • Bax
  • Bad
  • radical

Footnotes

  • ↵* Present address: Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA94305, U.S.A.

  • ↵** Summer-time student of Faculty of Pharmaceutical Sciences, Josai University, Japan

  • Received December 30, 2004.
  • Accepted April 4, 2005.
  • Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 25 (3B)
Anticancer Research
Vol. 25, Issue 3B
1 May 2005
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Tumor-specific Cytotoxicity of 3,5-Dibenzoyl-1,4-dihydropyridines
SUFI REZA M.D. MORSHED, KEN HASHIMOTO, YUKIE MUROTANI, MASAMI KAWASE, ANAMIK SHAH, KAZUE SATOH, HIROTAKA KIKUCHI, HIROFUMI NISHIKAWA, JUN MAKI, HIROSHI SAKAGAMI
Anticancer Research May 2005, 25 (3B) 2033-2038;

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Tumor-specific Cytotoxicity of 3,5-Dibenzoyl-1,4-dihydropyridines
SUFI REZA M.D. MORSHED, KEN HASHIMOTO, YUKIE MUROTANI, MASAMI KAWASE, ANAMIK SHAH, KAZUE SATOH, HIROTAKA KIKUCHI, HIROFUMI NISHIKAWA, JUN MAKI, HIROSHI SAKAGAMI
Anticancer Research May 2005, 25 (3B) 2033-2038;
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