Induction of Apoptosis by Tosyl-JM3 in HL-60 cells

  • Kim Kun-Jung (Division of Natural Science and Techology, College of Natural Science) ;
  • Ju Sung-Min (Division of Natural Science and Techology, College of Natural Science) ;
  • Lee Chai-Ho (Division of Natural Science and Techology, College of Natural Science) ;
  • Kim Won-Sin (Division of Natural Science and Techology, College of Natural Science) ;
  • Yun Yong-Gab (Department of Oriental medical Prescription. Wonkwang University) ;
  • Jeong Han-Sol (Department of Pathology, College of Oriental Medicine, Woosuk University) ;
  • Kim Sung-Hoon (Department of Oncology, Graduate School of East-West Medical Science) ;
  • Park Sung-Joo (Department of Herbology, College of Oriental Medicine, Wonkwang University) ;
  • Jeon Byung-Hun (Department of Pathology, College of Oriental Medicine, Wonkwang University)
  • Published : 2005.10.01

Abstract

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 $60{\mu}g/m{\ell}$) 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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