Echinomycin, typical DNA minor groove binder had comparable efficacy compared to 5-FU in phase II trial for colon cancer treatment. To improve echinomycin's drawback, we synthesized YK-2000 series (echinomycin analogues). Echinomycin and YK-2000 enabled to induce the apoptosis on HT-29 colorectal cancer cell line. Apoptosis in HT-29 cell triggered by echinomycin and YK-2000 were proven through DNA laddering, PARP (poly-(ADP-ribose) polymerase) cleavage and flow cytometric analysis. Such an apoptotic pattern displayed by YK-2000 was quite different from that of echinomycin. Next, to explore signaling pathway of echinomycin and YK-2000, we examined phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAP kinase. However, it is not clearly that the mechanism of cancer cell death induced by echinomycin and YK-2000. Here, we report that one of major apoptotic signaling pathway induced by echinomycin and YK-2000 may be MAP kinase pathway in HT-29 human colon cancer cells.

Keywords: Echinomycin, YK-2000, Apoptosis, MAP kinase, PARP