Molecular mechanisms involved in the antiproliferative action of protein tyrosine phosphatase inhibitor potassium bisperoxo(1,10-phenanthroline)oxovanadate
J. Ban et al., Molecular mechanisms involved in the antiproliferative action of protein tyrosine phosphatase inhibitor potassium bisperoxo(1,10-phenanthroline)oxovanadate, LIFE SCI, 68(2), 2000, pp. 165-175
Potassium bisperoxo(1,10-phenanthroline)oxovanadate, bpV(phen), a powerful
protein phosphotyrosine phosphatase inhibitor and a potent insulinomimetic,
influenced three fundamental cellular processes in HL-60 human leukemic ce
lls: 1) inhibition of proliferation, 2) induction of differentiation and 3)
apoptotic cell death. In the presence of micromolar concentrations of bpV(
phen) cell number and DNA synthesis decreased progressively with time of in
cubation. A single treatment with bpV(phen) (3 muM) activated a differentia
tion program; after 6 days of incubation 82% of cells were differentiated,
but differentiation started already within the first 24 h. Concentrations o
f 5-10 muM bpV(phen) caused the characteristic DNA ladder pattern, starting
after 4.5 h. Differentiation in HL-60 cells appear to be associated with a
ctivation of extracellular signal-regulated kinase while apoptosis is conne
cted with phosphorylation and activation of both extracellular signal-regul
ated kinase and c-Jun N-terminal kinase in a concentration and time-depende
nt manner. The antiproliferative and apoptotic action of bpV(phen) could be
exploited in combination chemotherapy in leukemia. (C) 2000 Elsevier Scien
ce Inc. All rights reserved.