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

12 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 1

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Echinomycin
HT29 Cells
Phosphotransferases
Apoptosis
JNK Mitogen-Activated Protein Kinases
Colonic Neoplasms
Mitogen-Activated Protein Kinase 11
Cell Line
Poly(ADP-ribose) Polymerases
DNA
Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
YK2000
Hydrophobic and Hydrophilic Interactions
Fluorouracil
Colorectal Neoplasms
Neoplasms
Cell Death
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Park, Ju Youn ; Park, Su Jung ; Shim, Kwang Yong ; Lee, Kyu Jae ; Kim, Yun Bong ; Kim, Yong Hae ; Kim, Soo Kie. / Echinomycin and a novel analogue induce apoptosis of HT-29 cells via the activation of MAP kinases pathway. In: Pharmacological Research. 2004 ; Vol. 50, No. 2. pp. 201-207.
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Echinomycin and a novel analogue induce apoptosis of HT-29 cells via the activation of MAP kinases pathway. / Park, Ju Youn; Park, Su Jung; Shim, Kwang Yong; Lee, Kyu Jae; Kim, Yun Bong; Kim, Yong Hae; Kim, Soo Kie.

In: Pharmacological Research, Vol. 50, No. 2, 01.08.2004, p. 201-207.

Research output: Contribution to journalArticle

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