MAPK signaling is involved in camptothecin-induced cell death

Seongeun Lee, Ho Soon Lee, Myungin Baek, Dae Yeon Lee, Yung Jue Bang, Hae Nyun Cho, Yun Sil Lee, Ji Hong Ha, Hae Yeong Kim, Doo Il Jeoung

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Camptothecin, a topoisomerase I inhibitor, is a well-known anticancer drug. However, its mechanism has not been well studied in human gastric cancer cell lines. Camptothecin induced apoptotic cell death in human gastric cancer cell line AGS. Z-VAD-fmk, pan-caspase inhibitor, blocked apoptotic phenotypes induced by Camptothecin suggesting that caspases are involved in camptothedn-induced cell death. An inhibitor of caspase-6 or -8 or -9 did not prevent cell death by camptothecin. Various protease inhibitors failed to prevent camptothecin-induced cell death. These results suggest that only few caspases are involved in camptothecin-induced cell death. Camptothecin induced phosphorylation of ERK1/2, JNK, and p38 MAPK, in a dose and time-dependent manner in AGS. Z-VAD-fmk did not affect MAPK signaling induced by camptothecin suggesting that caspase signaling occurs downstream of MAPK signaling. Blocking of p38 MAPK, but not ERK1/2, resulted in partial inhibition of cell death and PARP cleavage by camptothecin in AGS. Taken together, MAPK signaling is associated with apoptotic cell death by camptothecin.

Original languageEnglish
Pages (from-to)348-354
Number of pages7
JournalMolecules and Cells
Volume14
Issue number3
StatePublished - Dec 2002

Keywords

  • AGS
  • Apoptosis
  • Camptothecin
  • MAPK

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