Echinomycin and a novel analogue induce apoptosis of HT-29 cells via the activation of MAP kinases pathway

Ju Youn Park, Su Jung Park, Kwang Yong Shim, Kyu Jae Lee, Yun Bong Kim, Yong Hae Kim, Soo Kie Kim

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Echinomycin, in typical DNA minor groove binder, had comparable efficacy compared to 5-FU in the phase II trail of colon cancer treatment. To improve echinomycin's drawback (hydrophobicity, toxicity), we synthesized the YK-2000 series (echinomycin analogues). Among these, YK-2000 had the best in vitro cytotoxicity on six different human solid cancer cell lines. Echinomycin and YK-2000 were enabled to induce the apoptosis on the HT-29 colorectal cancer cell line. The hypothesis that apoptosis in the HT-29 cell was triggered by echinomycin and YK-2000 were supported through DNA laddering, poly-(ADP-ribose) polymerase (PARP) cleavage, and flow cytometric analysis. In order to explore the signaling pathway of echinomycin and YK-2000, we examined the 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, what the mechanism of cancer cell death would be induced by echinomycin and YK-2000 is unknown. Here, we present some evidence that one of the major apoptotic signaling pathways induced by echinomycin and YK-2000 is possibly the MAP kinases pathway in HT-29 human colon cancer cells.

Original languageEnglish
Pages (from-to)201-207
Number of pages7
JournalPharmacological Research
Volume50
Issue number2
DOIs
Publication statusPublished - 2004 Aug

All Science Journal Classification (ASJC) codes

  • Pharmacology

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