RRC ID 77506
Author Hong J, Ishihara K, Zee O, Ohuchi K.
Title Induction of apoptosis by apicularen A in human promyelocytic leukemia cell line HL-60.
Journal Planta Med
Abstract Apicularen A, a macrolide isolated from the myxobacterial genus Chondromyces, suppressed the proliferation of human promyelocytic leukemia cells (HL-60 cells), increased the release of lactate dehydrogenase and induced condensation and fragmentation of chromatin at 1 to 100 nM. In addition, it induced the DNA fragmentation, increased the percentage of annexin V-stained cells, and cleaved poly(ADP-ribose) polymerase (PARP), a substrate of caspase. In contrast, apicularen B, an N-acetylglucosamine glycoside of apicularen A, had no such effects at 100 nM. These findings indicated that apicularen A induces apoptosis in HL-60 cells by activating caspases. Phosphorylation of p44/42 MAPK, p38 MAPK and Akt was not induced by apicularen A at 100 nM, suggesting that the apicularen A-induced apoptosis in HL-60 cells is not regulated by the activation of p44/42 MAPK, p38 MAPK or Akt. Furthermore, by acridine orange staining of the cells, it was suggested that apicularen A but not apicularen B inhibits vacuolar-type H+-ATPase.
Volume 71(4)
Pages 306-12
Published 2005-4-1
DOI 10.1055/s-2005-864095
PMID 15856405
MeSH Antineoplastic Agents, Phytogenic / administration & dosage Antineoplastic Agents, Phytogenic / pharmacology* Antineoplastic Agents, Phytogenic / therapeutic use Apoptosis / drug effects Bridged Bicyclo Compounds, Heterocyclic / administration & dosage Bridged Bicyclo Compounds, Heterocyclic / pharmacology* Bridged Bicyclo Compounds, Heterocyclic / therapeutic use DNA Fragmentation / drug effects Flow Cytometry HL-60 Cells / drug effects Humans Leukemia, Myeloid / drug therapy Macrolides / administration & dosage Macrolides / pharmacology* Macrolides / therapeutic use Phytotherapy*
IF 2.687
Human and Animal Cells HL60(RCB0041)