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KMID : 1123920050190030802
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Korean Journal of Oriental Physiology and Pathology
2005 Volume.19 No. 3 p.802 ~ p.810
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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
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Ju Sung-Min
Kim Kun-Jung
Lee Jong-Gil
Lee Chai-Ho
Han Dong-Min
Yun Young-Gab
Hong Gi-Yun
An Won-Gun
Jeon Byung-Hoon
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Abstract
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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 . 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.
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KEYWORD
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CDST, Tetrahydroisoquinoline, Apoptosis, HL-60
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