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HT-29 ¼¼Æ÷ÀÇ ¼¼Æ÷°í»ç¸¦ À¯µµÇÏ´Â Echinomycin°ú ±× »õ·Î¿î À¯µµÃ¼ÀÇ MAP Kinase ½ÅÈ£Àü´Þ°æ·ÎÀÇ ¿ªÇÒ The Role of MAP Kinase Pathways in Echinomycin and Vovel Analogue-induced Apoptosis of HT-29 Cells

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¹Ú¼öÁ¤, Park Ju-Youn, ½É±¤¿ë, Kim Yun-Bong, ±è¼ºÈ£, ±è¿ëÇØ, ±è¼ö±â,
¼Ò¼Ó »ó¼¼Á¤º¸
¹Ú¼öÁ¤ ( Park Su-Jung ) 
¿¬¼¼´ëÇб³ ¿øÁÖÀÇ°ú´ëÇÐ ¹Ì»ý¹°Çб³½Ç

 ( Park Ju-Youn ) 
¿¬¼¼´ëÇб³ ¿øÁÖÀÇ°ú´ëÇÐ ¹Ì»ý¹°Çб³½Ç
½É±¤¿ë ( Shim Kwang-Yong ) 
¿¬¼¼´ëÇб³ ¿øÁÖÀÇ°ú´ëÇÐ ³»°úÇб³½Ç
 ( Kim Yun-Bong ) 
KAIST È­Çаú
±è¼ºÈ£ ( Kim Seong-Ho ) 
KAIST È­Çаú
±è¿ëÇØ ( Kim Yong-Hae ) 
KAIST È­Çаú
±è¼ö±â ( Kim Soo-Kie ) 
¿¬¼¼´ëÇб³ ¿øÁÖÀÇ°ú´ëÇÐ ¹Ì»ý¹°Çб³½Ç

Abstract


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.

Å°¿öµå

Echinomacin;YK-2000;Apoptosis;MAP kINASE;PARP

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