Induction of apoptosis by apicularen A in human promyelocytic leukemia cell line HL-60

• Published in: Planta medica Vol. 71; no. 4; p. 306
• Main Authors: Hong, Jangja, Ishihara, Kenji, Zee, Okpyo, Ohuchi, Kazuo
• Format: Journal Article
• Language: English
• Published: Germany 01-04-2005
• Subjects: 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
• ISSN: 0032-0943
• DOI: 10.1055/s-2005-864095

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.