Cytotoxic and apoptotic activites of echinomycin derivative (echinomycin-7) on P388 murine leukemia cells

Hyang Jeon, Sung Su Kim, Yoon Suk Kim, Yil Sung Park, Yong Hae Kim, Sun Ju Choi, Soo Kie Kim, Tae Ue Kim

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Abstract

Echinomycin-7 is an echinomycin derivative, S-methylated 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 IC50 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 G1/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.

Original languageEnglish
Pages (from-to)560-564
Number of pages5
JournalJournal of Biochemistry and Molecular Biology
Volume31
Issue number6
Publication statusPublished - 1998 Nov 30

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Jeon, H., Kim, S. S., Kim, Y. S., Park, Y. S., Kim, Y. H., Choi, S. J., Kim, S. K., & Kim, T. U. (1998). Cytotoxic and apoptotic activites of echinomycin derivative (echinomycin-7) on P388 murine leukemia cells. Journal of Biochemistry and Molecular Biology, 31(6), 560-564.