Cytotoxic and Apoptotic Activites of Echinomycin Derivative (Echinomycin-7) on P388 Murine Leukemia Cells

  • Jeon, Hyang (Department of Medical Technology, College of Health Science, Yonsei University) ;
  • Kim, Sung-Su (Department of Medical Technology, College of Health Science, Yonsei University) ;
  • Kim, Yoon-Suk (Department of Medical Technology, College of Health Science, Yonsei University) ;
  • Park, Yil-Sung (Department of Chemistry, KAIST) ;
  • Kim, Yong-Hae (Department of Chemistry, KAIST) ;
  • Choi, Sun-Ju (Department of Microbiology, Wonju College of Medicine, Yonsei University) ;
  • Kim, Soo-Kie (Department of Microbiology, Wonju College of Medicine, Yonsei University) ;
  • Kim, Tae-Ue (Department of Medical Technology, College of Health Science, Yonsei University)
  • Received : 1998.06.22
  • Accepted : 1998.08.01
  • Published : 1998.11.30

Abstract

Echinomycin-7 is an echinomycin derivative, Smethylated sulfonium perchlorate of echinomycin. We studied the in vitro cytotoxicity and in vivo antitumor activity of echinomycin-7 against P388 leukemia cells and compared the results with echinomycin. With respect to the cytotoxic effects, echinomycin-7 had cell line-dependent $IC_{50}$ values while echinomycin had similar values to several tumor cell lines. Also, in vivo antitumor activities were observed in tumor-bearing mice treated with both agents, which showed that echinomycin-7 had a broad therapeutic dose range. We also observed the apoptosis on leukemia cells treated with echinomycin-7 which exihibited the ladder pattern of DNA on electrophoresis. In addition to apoptosis, echinomycin-7 arrested $G_1/S$ phases of the cell cycle at the same time. We then examined the signaling pathway of echinomycin-7-induced apoptosis and showed that ERK of the MAP kinase family was activated and translocated into the nucleus by echinomycin-7 stimulation. This study suggests that echinomycin-7 acts as an antitumor agent through in vitro cytotoxicity and has in vivo antitumor activity against leukemia cells, and that the echinomycin-7- induced apoptosis might involve signal transduction via MAP kinases.

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