KMID : 1123920050190051370
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Korean Journal of Oriental Physiology and Pathology 2005 Volume.19 No. 5 p.1370 ~ p.1374
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Induction of Apoptosis by Tosyl-JM3 in HL-60 cells
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Kim Kun-Jung
Ju Sung-Min Lee Chai-Ho Kim Won-Sin Yun Young-Gab Jeong Han-Sol Kim Sung-Hoon Park Sung-Joo Jeon Byung-Hoon
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Abstract
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The Tosyl-JM3 (TJM3) is a modified compound from one of 1,2,3,4-Tetra- hydroisoquinoline (THIQ) derivatives. The THIQs include potent cytotoxic agents that display a range of anti-tumor activities, antimicrobial activity, and other biological properties. In this study, we investigated the effect of TJM3 on the cytotoxicity, induction of apoptosis in human promyelocytic leukemia cells (HL-60 cells). TJM3 showed a significant cytotoxic activity in HL-60 cells (IC50 = approximately ) after a 24 hr incubation. Treatment of HL-60 cells with TJM3 exhibited 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 TJM3 caused a decrease of procaspase-3 protein. Further molecular analysis demonstrated that TJM3 led to cleavage of poly(ADP-ribose) polymerase (PARP) by western blot and increase of hypodiploid (Sub-G1) population in the flow cytometric analysis. In conclusion, these above results indicate that TJM3 dramatically suppresses HL-60 cell growth and induces apoptosis. These data may support a possibility for the use of TJM3 in the prevention and treatment of leukemia.
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KEYWORD
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Apoptosis, TJM3, caspase-3, PARP
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