S-trityl-L-cysteine derivative induces caspase-independent cell death in K562 human chronic myeloid leukemia cell line.
Effect of CF(3)-STLC, a potent kinesin spindle protein (KSP) inhibitor, on K562 human CML cell line was investigated. Treatment with CF(3)-STLC induced mitotic arrest of the cell cycle with the appearance of characteristic monoastral spindles, subsequent apoptotic cell death and cleavage of PARP-1, caspase-3, and 4E-BP1. The wide ranging caspase inhibitor z-VAD fmk prevented the cleavage of caspase-3 and 4E-BP1, but failed to attenuate PARP-1 cleavage or cell death triggered by CF(3)-STLC. These results suggest that CF(3)-STLC can induce apoptotic cell death in a caspase-independent manner, and may work effectively as an anti-cancer agent for hematological malignancies.
Shimizu
Makiko
M
Center for Drug Discovery, School of Pharmaceutical Science, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Ishii
Hirosuke
H
Ogo
Naohisa
N
Unno
Yuka
Y
Matsuno
Kenji
K
Sawada
Jun-Ichi
J
Akiyama
Yasuto
Y
Asai
Akira
A
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
C003724:3-tritylthio-L-alanine; D020169:Caspases; D003545:Cysteine