RRC ID 42028
著者 Hong J, Yamaki K, Ishihara K, Ahn JW, Zee O, Ohuchi K.
タイトル Induction of apoptosis of RAW 264.7 cells by the cytostatic macrolide apicularen A.
ジャーナル J Pharm Pharmacol
Abstract In RAW 264.7 cells, a mouse leukaemic monocyte cell line, apicularen A decreased cell growth and survival as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in a concentration-dependent manner at 10-1000 nM. Apicularen B, an N-acetyl-glucosamine glycoside of apicularen A, was 10-100-fold less effective than apicularen A. Apicularen A induced a DNA ladder, an increase in the percentage of sub-G(1) cells and annexin V-binding cells, and promoted the activation of caspase as revealed by the cleavage of poly(ADP-ribose) polymerase, indicating that apicularen A induced apoptosis in RAW 264.7 cells. In addition, apicularen A phosphorylated p44/42 mitogen-activated protein kinase (MAPK) and p38 MAPK. The p44/42 MAPK inhibitor PD98059 rescued the cells from apicularen-induced decrease in cell growth and survival as determined by the MTT assay, while the p38 MAPK inhibitor SB203580 augmented the effect of apicularen A. This suggested the activation of p44/42 MAPK to be pro-apoptotic and the activation of p38 MAPK antiapoptotic in apicularen A-treated RAW 264.7 cells.
巻・号 55(9)
ページ 1299-306
公開日 2003-9-1
DOI 10.1211/0022357021639
PMID 14604474
MeSH Animals Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Apoptosis / drug effects* Bridged Bicyclo Compounds, Heterocyclic / chemistry Bridged Bicyclo Compounds, Heterocyclic / pharmacology* Caspases / metabolism Cell Line Cell Proliferation / drug effects Cell Survival / drug effects DNA Fragmentation / drug effects Dose-Response Relationship, Drug Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology Flow Cytometry G1 Phase / drug effects Imidazoles / pharmacology Macrolides / chemistry Macrolides / pharmacology* Macrophages / cytology Macrophages / drug effects Macrophages / metabolism Mice Molecular Structure Organic Chemicals / pharmacology Phosphorylation / drug effects Pyridines / pharmacology p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors p38 Mitogen-Activated Protein Kinases / metabolism
IF 2.571
引用数 20
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞