RRC ID 37837
著者 Hashimoto K, Suzuki F, Sakagami H.
タイトル Declined asparagine synthetase mRNA expression and enhanced sensitivity to asparaginase in HL-60 cells committed to monocytic differentiation.
ジャーナル Anticancer Res
Abstract During 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiation of human promyelocytic leukemia HL-60 cells toward maturing monocytes/macrophages, asparagine synthetase (ASNS) mRNA expression declined time and dose-dependently. The effect of TPA was inhibited by inhibitors for PKC and MEK 1/2, but not by those for JNK and p38 MAPK. Combination treatment with TPA and asparaginase synergistically enhanced the growth retardation accompanied by apoptotic cell death characterized by internucleosomal DNA fragmentation. These data suggest the possible involvement of MEK1/2 MAPK in the inhibitory effect of TPA on ASNS mRNA expression and that the induction of the down-regulation of ASNS (via MEK1/2 activation) may be a new strategy for the treatment of leukemia blast cells.
巻・号 29(4)
ページ 1303-8
公開日 2009-4-1
PII 29/4/1303
PMID 19414379
MeSH Antineoplastic Agents / pharmacology* Apoptosis / drug effects Asparaginase / pharmacology* Aspartate-Ammonia Ligase / antagonists & inhibitors Aspartate-Ammonia Ligase / genetics* Aspartate-Ammonia Ligase / metabolism Cell Differentiation* Drug Synergism Drug Therapy, Combination HL-60 Cells / metabolism Humans JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors JNK Mitogen-Activated Protein Kinases / metabolism MAP Kinase Kinase Kinases / antagonists & inhibitors MAP Kinase Kinase Kinases / metabolism Monocytes / cytology Protein Kinase C / antagonists & inhibitors Protein Kinase C / metabolism Proto-Oncogene Proteins / antagonists & inhibitors Proto-Oncogene Proteins / metabolism RNA, Messenger / genetics* RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Tetradecanoylphorbol Acetate / pharmacology p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors p38 Mitogen-Activated Protein Kinases / metabolism
IF 1.994
引用数 9
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 HL60(RCB0041)