Angelmicin B, a new inhibitor of oncogenic signal transduction, inhibits growth and induces myelomonocytic differentiation of human myeloid leukemia HL-60 cells.

Abstract

Angelmicin B is a new microbial substance which inhibits src tyrosine kinase activity and oncogenic signal transduction. We investigated the effect of angelmicin B on the proliferation and differentiation of the HL-60 human myeloid leukemia cell line. Angelmicin B caused the dose-dependent inhibition of cell proliferation and induction of differentiation along the myelomonocytic pathway, as determined by morphological changes, nitroblue tetrazolium (NBT) reduction, and non-specific esterase and lysozyme activities at concentrations ranging from 0.1 to 0.5 microgram/ml. Also, it induced significantly the differentiation of mouse myeloid leukemia M1 cells. A similar concentration of angelmicin B inhibited the growth of the myeloid leukemia cell lines K562, HEL, KU812, ML-1, U937 and THP-1, but did not induce differentiation of these cells significantly. The differentiation of HL-60 cells was enhanced by combined treatment with angelmicin B and 1 alpha, 25-dihydroxyvitamin D3 (VD3), retinoic acid or tumor necrosis factor-alpha (TNF alpha). Angelmicin analogs (A1, A2, B, C and D) had almost equivalent effects on the differentiation of HL-60 cells, although angelmicins C and D inhibited src tyrosine kinase activity less than the other analogs. The effective concentrations of angelmicin B in src kinase inactivation was about 100-fold higher than those required for the growth inhibition and differentiation induction. These findings indicate that the differentiation-inducing activity of angelmicins is not associated with their src kinase-inhibiting activity, and may be associated with the modulation of other signal pathway(s).

• Authors: A Yokoyama, J Okabe-Kado, Y Uehara, T Oki, S Tomoyasu, N Tsuruoka, Y Honma
• Journal: Leukemia research (Leuk Res) Vol. 20 Issue 6 Pg. 491-7 (Jun 1996) ISSN: 0145-2126 [Print] England
• PMID: 8709621 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthraquinones
• Antibiotics, Antineoplastic
• Tumor Necrosis Factor-alpha
• angelmicin B
• Cholecalciferol
• Nitroblue Tetrazolium
• Tretinoin
• Protein-Tyrosine Kinases

Topics

• Animals
• Anthraquinones (pharmacology)
• Antibiotics, Antineoplastic (pharmacology)
• Cell Differentiation (drug effects)
• Cell Division (drug effects)
• Cholecalciferol (pharmacology)
• HL-60 Cells (drug effects, pathology)
• Humans
• Leukemia, Myeloid (drug therapy, genetics, pathology)
• Mice
• Monocytes (cytology, drug effects)
• Nitroblue Tetrazolium
• Oncogenes
• Protein-Tyrosine Kinases (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• Tretinoin (pharmacology)
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (pharmacology)