title: S-trityl-L-cysteine derivative induces caspase-independent cell death in K562 human chronic myeloid leukemia cell line.
abstract: 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.
authors.affiliation: Center for Drug Discovery, School of Pharmaceutical Science, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Shimizu
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Ishii
authors.forename: Naohisa
authors.initials: N
authors.lastname: Ogo
authors.forename: Yuka
authors.initials: Y
authors.lastname: Unno
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuno
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sawada
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Akira
authors.initials: A
authors.lastname: Asai
mesh_terms: 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
chemical_list: C003724:3-tritylthio-L-alanine; D020169:Caspases; D003545:Cysteine