Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
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CDST, a Derivative of Tetrahydroisoquinoline, Induced Apoptosis in HL-60 Cells through Activation of Caspase-8, Bid Cleavage and Cytochrome c Release

  • Ju, Sung-Min (Department of Pathology, College of Oriental Medicine, Wonkwang University) ;
  • Kim, Kun-Jung (Department of Pathology, College of Oriental Medicine, Wonkwang University) ;
  • Lee, Jong-Gil (Department of Pathology, College of Oriental Medicine, Wonkwang University) ;
  • Lee, Chai-Ho (Division of Natural Science and Technology, College of Natural Sciences, Wonkwang University) ;
  • Han, Dong-Min (Division of Natural Science and Technology, College of Natural Sciences, Wonkwang University) ;
  • Yun, Young-Gab (Department of Prescription, College of Oriental Medicine, Wonkwang University) ;
  • Hong, Gi-Yun (Department of Obstetric and Gynecology, College of Medicine, Wonkwang University) ;
  • An, Won-Gun (Department of Oral Pathology, College of Dentistry, Pusan National Universsity) ;
  • Jeon, Byung-Hun (Department of Pathology, College of Oriental Medicine, Wonkwang University)
  • Published : 2005.06.25
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Abstract

The tetrahydroisoquinolines included potent cytotoxic agents that showed antitumor activity,antimicrobial activity, and other biological properties. We studied the effect of CDST, 1-Chloromethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonic acid amide, a newly synthesized anti-cancer agent. The cytotoxic activity of CDST in HL-60 cells was increased in a dose-dependent manner. CDST, tetrahydroisoquinolines derivative, was cytotoxic to HL-60 cells, with IC50 of $80{\mu}g/ml$. Treatment of CDST to HL-60 cells showed the fragmentation of DNA in a dose- and time dependent manner, suggesting that thesecells underwent apoptosis. Treatment of HL-60 cells with CDST was induced in a dose- and time-dependent activation of caspase-3, caspase-8 and proteolytic cleavage of poly(ADP-ribose) polymerase. In caspase activity assay, caspase-3 and -8 was activated after 12 h and 6 h posttreatment, respectively. CDST also caused the release of cytochrome c from mitochondria into the cytosol. CDST-induced cytochrome c release was mediated by caspase-8-dependent cleavage of Bid and Bax translocation. These results suggest that caspase-8 induced Bid cleavage and Bax translocation, caused mitochondrial cytochrome c release, and induce caspase-3 activationduring CDST-induced apoptosis in HL-60 cells.

Keywords

References

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