PMID- 8709621
OWN - NLM
STAT- MEDLINE
DCOM- 19960910
LR  - 20190826
IS  - 0145-2126 (Print)
IS  - 0145-2126 (Linking)
VI  - 20
IP  - 6
DP  - 1996 Jun
TI  - Angelmicin B, a new inhibitor of oncogenic signal transduction, inhibits growth 
      and induces myelomonocytic differentiation of human myeloid leukemia HL-60 cells.
PG  - 491-7
AB  - 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).
FAU - Yokoyama, A
AU  - Yokoyama A
AD  - Department of Chemotherapy, Saitama Cancer Center Research Institute, Japan.
FAU - Okabe-Kado, J
AU  - Okabe-Kado J
FAU - Uehara, Y
AU  - Uehara Y
FAU - Oki, T
AU  - Oki T
FAU - Tomoyasu, S
AU  - Tomoyasu S
FAU - Tsuruoka, N
AU  - Tsuruoka N
FAU - Honma, Y
AU  - Honma Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - 0 (Anthraquinones)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 151687-86-4 (angelmicin B)
RN  - 1C6V77QF41 (Cholecalciferol)
RN  - 298-83-9 (Nitroblue Tetrazolium)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Anthraquinones/*pharmacology
MH  - Antibiotics, Antineoplastic/*pharmacology
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Cholecalciferol/pharmacology
MH  - HL-60 Cells/drug effects/pathology
MH  - Humans
MH  - Leukemia, Myeloid/*drug therapy/genetics/pathology
MH  - Mice
MH  - Monocytes/cytology/drug effects
MH  - Nitroblue Tetrazolium
MH  - Oncogenes
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism
MH  - Signal Transduction/*drug effects
MH  - Tretinoin/pharmacology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1996/06/01 00:00
MHDA- 1996/06/01 00:01
CRDT- 1996/06/01 00:00
PHST- 1996/06/01 00:00 [pubmed]
PHST- 1996/06/01 00:01 [medline]
PHST- 1996/06/01 00:00 [entrez]
AID - 0145-2126(96)00014-8 [pii]
AID - 10.1016/0145-2126(96)00014-8 [doi]
PST - ppublish
SO  - Leuk Res. 1996 Jun;20(6):491-7. doi: 10.1016/0145-2126(96)00014-8.