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KMID : 0603520030080020063
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Journal of Korean Association of Cancer Prevention
2003 Volume.8 No. 2 p.63 ~ p.72
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The Role of MAP Kinase Pathways in Echinomycin and Vovel Analogue-induced Apoptosis of HT-29 Cells
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Park Su-Jung
Park Ju-Youn
Shim Kwang-Yong
Kim Yun-Bong
Kim Seong-Ho
Kim Yong-Hae
Kim Soo-Kie
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Abstract
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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 inase pathway in HT-29 human colon cancer cells.
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KEYWORD
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Echinomacin, YK-2000, Apoptosis, MAP kINASE, PARP
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