SPECIFIC FUNCTION OF STAT5 IN REGULATION OF PROLIFERATION OF CHRONIC LEUKEMIA K562 CELLS: INHIBITORY EFFECT OF WHI-P131
E. V. Mityushova, N. D. Aksenov, I. I. Marakhova 1
Institute of Cytology RAS, St. Petersburg;
1 e-mail: iim@mail.cytspb.rssi.ru
In this study, we examined the possible role of JAK/STAT signaling pathway in regulation of proliferation of chronic leukemia cells K562. The thyrosine phosphorylation of
STAT3 and STAT5 was used as a marker of an activation status of STAT proteins. We demonstrate that in growing culture of K562 both STAT3 and STAT5 are constitutively
activated. To determine the significance of STATs activity in maintaining the high level of K562 proliferation we tested two JAK inhibitors: AG-490 (JAK2 and JAK3 inhibitor) and
WHI-P131 (a new specific JAK3 inhibitor). We showed that in long-tern cultures (48 h) of K562 cells with AG-490 or WHI-P131 the cells remain viable. It was found that
treatment with WHI-P131 (30-100 μM) decreased the thyrosine phosphorylation of STAT5 being without effect on the high level of STAT3 phosphorylation. In proliferating
K562 cells, AG-490 (25-50 μM) did not influence STAT3 and STAT5 phosphorylation. The flow cytometry analysis revealed a dose-dependent decrease in
G1 and S phases and an increase in G2/M phases in WHI-P131-treated K562 cell cultures and no
changes in cell cycle structure in AG-490-treated cells. Thus, our findings indicate a preferential role for STAT5 (not constitutively active STAT3) in proliferation of leukemia to
other JAK drugs which stimulate apoptosis and decrease proliferation, WHI-P131 prevents K562 cells growth by arresting in G2/M phases
of cell cycle.
Key words: JAK/STAT signaling, STAT3, STAT5, WHI-P131, AG-490, proliferation, K562 cells
| Pdf |
Back |
Contents |
Main |