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 language | English |
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Pages (from-to) | 560-564 |
Number of pages | 5 |
Journal | Journal of biochemistry and molecular biology |
Volume | 31 |
Issue number | 6 |
Publication status | Published - 1998 Nov 30 |
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology