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KMID : 1123920050190030772
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Korean Journal of Oriental Physiology and Pathology
2005 Volume.19 No. 3 p.772 ~ p.778
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In vitro Cytotoxicity and Apoptotic Effect of Chloromethyl-2-dihydroxyphosphinyl-6,7-dimethoxy-1,2,3,4- tetrahydroisoquinoline on HL-60 Cells
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Kim Kun-Jung
Ju Sung-Min
Kim Myung-Wan
Lee Chai-Ho
Kim Won-Sin
Yun Young-Gab
Yun Yoo-Sik
Jeon Byung-Hoon
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Abstract
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The chloromethyl-2-dihydroxyphosphinyl-6,7-dimethoxy-1,2,3,4-tetrahydro- isoquinoline (CDDT) is a newly synthesized derivative from 1,2,3,4-Tetra- hydroisoquinoline (THIQ). The THIQs include potent cytotoxic agents that display a range of antitumor activities, antimicrobial activity, and other biological properties. In this study, we investigated the effect of CDDT on the cytotoxicity, induction of apoptosis in human promyelocytic leukemia cells (HL-60 cells). CDDT showed a significant cytotoxic activity in HL-60 cells ( = approximately ) at a 24 hr incubation. Treatment of HL-60 cells with CDDT displayed several features of apoptosis, including formation of DNA ladders in agarose gel electrophoresis, morphological changes of HL-60 cells with DAPI stain. Here we observed that CDDT caused activation of caspase-3, caspase-8, and caspase-9. The most efficacious time on the activation of caspases-3 was achieved at 12 hr. Further molecular analysis demonstrated that CDDT led to cleavage of poly(ADP-ribose) polymerase (PARP), increase of hypodiploid (Sub-G1) population in the flow cytometric analysis. In conclusion, these above results indicate that CDDT dramatically suppresses HL-60 cell growth by activation of caspase-3 with caspase-8, -9 activity. These data may support a pivotal mechanism for the use of CDDT in the prevention and treatment of leukemia.
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KEYWORD
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Apoptosis, CDDT, caspase-8, caspase-9, caspase-3
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