Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Pharmacodynamics of CKD-602 (Belotecan) in 3D Cultures of Human Colorectal Carcinoma Cells

  • Lee Sin-Hyung (Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea) ;
  • Al-Abd Ahmed M. (Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea) ;
  • Park Jong-Kook (Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea) ;
  • Cha Jung-Ho (Department of Anatomy, College of Medicine, The Catholic University of Korea) ;
  • Ahn Soon-Kil (CKD Research Institute) ;
  • Kim Joon-Kyum (CKD Research Institute) ;
  • Kuh Hyo-Jeong (Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea)
  • Published : 2006.06.01
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Abstract

CKD-602 exerts its antitumor effect via inhibition of topoisomerase I in cancer cells. Multicellular spheroid (MCS) and Multicellular layers (MCLs) are known as in vitro 3-dimensional models which closely represent tumor conditions in vivo. In order to investigate the potential of CKD-602 against human colorectal tumors, we evaluated the anti-proliferative activity and penetration ability of CKD-602 in MCS and MCL cultures of DLD-l human colorectal cancer cells, respectively. The maximum effects($E_{max}$) induced by CKD-602 were significantly lower in MCS compared to monolayers (48% vs 92%). With prolonged drug exposure, the $IC_{50's}$ of CKD-602 decreased to $23.5{\pm}1.0nM$ in monolayers after 24 h exposure and $42.3{\pm}1.7nM$ in MCS after 6 days, respectively. However, no further increase in effect was observed for exposure time longer than growth doubling time (Td) in both cultures. Activity of CKD-602 was significantly reduced after penetration through MCL and also with cell-free insert membrane. In conclusion, CKD-602 showed significantly decreased anti-proliferative activity in 3D cultures (MCS) of human colorectal cancer cells. Tumor penetration of CKD-602 could not be determined due to loss of activity after penetration through cell free insert membrane, which warrants further evaluation using a modified model.

Keywords

References

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