RRC ID 71745
著者 Nomura Y, Inanami O, Takahashi K, Matsuda A, Kuwabara M.
タイトル 2-Chloro-2'-deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT-4.
ジャーナル Leukemia
Abstract The mechanism of apoptosis induced by 2-chloro-2'-deoxyadenosine (2CdA) in human leukemia cell line MOLT-4 was investigated. 2CdA induced increases of 3'-OH ends of genomic DNA, ladder-like DNA fragmentation and phosphatidylserine translocation to the outer membrane, which are apoptotic characteristics. These apoptotic phenomena induced by 2CdA were inhibited by cycloheximide (CHX; a protein synthesis inhibitor), deoxycytidine (dC; a substrate of deoxycytidine kinase), acetyl Ile-Glu-Thr-Asp aldehyde (Ac-IETD-CHO; a caspase-8 inhibitor) and acetyl Asp-Glu-Val-Asp aldehyde (Ac-DEVD-CHO; a caspase-3 inhibitor). The protein synthesis-dependent expression of Fas and Fas ligand (Fas-L) was detected by treatment with 2CdA. The proteolytic processing of procaspases-8 and -3 to produce active fragments, caspases-8 (p18) and -3 (p17), respectively, was observed after treatment with 2CdA, and suppressed by cycloheximide. Increases in the activities of caspases-8 and -3 were observed after 2CdA treatment. Their activation was also dependent on protein synthesis. These results indicated that 2CdA-induced apoptosis was triggered by phosphorylation of 2CdA followed by the protein synthesis-dependent expression of Fas and Fas-L and activation of caspases-8 and -3.
巻・号 14(2)
ページ 299-306
公開日 2000-2-1
DOI 10.1038/sj.leu.2401649
PMID 10673748
MeSH Antineoplastic Agents / antagonists & inhibitors Antineoplastic Agents / pharmacology* Apoptosis / drug effects* Blotting, Western Caspase 3 Caspase 8 Caspase 9 Caspase Inhibitors Caspases / metabolism* Cladribine / antagonists & inhibitors Cladribine / pharmacology* Cycloheximide / pharmacology Cysteine Proteinase Inhibitors / pharmacology DNA Fragmentation DNA, Neoplasm Deoxycytidine / pharmacology Enzyme Activation / drug effects Flow Cytometry Fluorometry Humans In Situ Nick-End Labeling Leukemia / drug therapy* Leukemia / enzymology Leukemia / metabolism* Oligopeptides / pharmacology Phosphorylation / drug effects Tumor Cells, Cultured fas Receptor / drug effects*
IF 8.665
リソース情報
ヒト・動物細胞 MOLT-4(RCB0206)