Naslov
Molecular mechanism involved in the antiproliferative action of protein tyrosine phosphatase inhibitor potassium bisperoxo(1, 10-phenanthroline)oxovanadate

Autori
Ban, Jasna ; Maysinger Dušica ; Kovač, Višnja ; Galetić, Ivana ; Matulić, Maja ; Hadžija, Mirko ; Užarević, Branka

Izvornik
Life sciences (0024-3205) 68 (2000), 2; 165-175

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
protein tyrosine phosphatases; peroxovanadium derivative; differentiation; cell cycle; apoptosis; HL-60 leukemia cells

Sažetak
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 cells: 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 incubation. A single treatment with bpV(phen) (3 uM) activated a differentiation program ; after 6 days of incubation 82% of cells were differentiated, but differentiation started already within the first 24 h. Concentrations of 5-10 uM bpV(phen) caused the characteristic DNA ladder pattern, starting after 4.5 h. Differentiation in HL-60 cells appear to be associated with activation of extracellular signal-regulated kinase while apoptosis is connected with phosphorylation and activation of both extracellular signal-regulated kinase and c-Jun N-terminal kinase in a concentration and time-dependent manner. The antiproliferative and apoptotic action of bpV(phen) could be exploited in combination chemotherapy in leukemia.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Javno zdravstvo i zdravstvena zaštita

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