MAPK signaling is involved in camptothecin-induced cell death.
Mol Cells
; 14(3): 348-54, 2002 Dec 31.
Article
in En
| MEDLINE
| ID: mdl-12521296
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 camptothecin-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.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stomach Neoplasms
/
Camptothecin
/
Signal Transduction
/
Apoptosis
/
Mitogen-Activated Protein Kinases
/
MAP Kinase Signaling System
/
JNK Mitogen-Activated Protein Kinases
/
Enzyme Inhibitors
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Mol Cells
Journal subject:
BIOLOGIA MOLECULAR
Year:
2002
Document type:
Article