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Different effects of phosphatidylinositol 3-kinase inhibitor LY294002 and Akt inhibitor SH-5 on cell cycle progression in synchronized HL-60 leukemia cells

Vesna LUKINOVIĆ-ŠKUDAR ; Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 3, 10 000 Zagreb, Croatia
HRVOJE BANFIĆ ; Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 3, 10 000 Zagreb, Croatia
DORA VIŠNJIĆ ; Department of Physiology and Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 3, 10 000 Zagreb, Croatia

Sažetak

Background and Purpose: Pharmacological inhibitors of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway have been proposed in treatment of leukemia. Our previous studies demonstrated that PI3K inhibitor LY294002 and Akt inhibitor SH-5 reduced the number of viable HL-60 leukemia cells, but exerted different effects on their differentiation. PI3K inhibitor LY294002 induced an arrest of HL-60 cells in G0/G1 and G2/M phases of the cell cycle, but the effects of Akt inhibitor on cell cycle progression have not been investigated. The present study was undertaken in
order to compare the effects of LY294002 and SH-5 on cell cycle progression in a model of aphidicolin and nocodazole-synchronized HL-60 cells.

Materials and Methods: HL-60 cells were arrested at G1/S phase by
aphidicolin, or G2/M phase by nocodazole, washed and allowed to progress synchronously through the cell cycle. PI3K inhibitor LY294002 (10 μM) and Akt inhibitor SH-5 (20 μM) were added to medium after release from the block. DNA content was determined by propidium iodide staining and flow cytometry.

Results: In aphidicolin-synchronizedHL-60 cells, LY294002 induced a
delay in progression through S andG2/M phases, while Akt inhibitor had no significant effects. No statistically significant effects were observed in LY294002 or SH-5-treated cells at 1–5 h after release from nocodazole block.

Conclusion: PI3K inhibitor LY294002 and Akt inhibitor SH-5, applied
at doses that effectively inhibit Akt-activity, have different effects on cell cycle progression in aphidicolin-synchronized HL-60 cells, suggesting that LY294002-induced delay in S and G2/M phase is probably not due to the specific inhibition of Akt-activity.

Ključne riječi

cell cycle; phosphatidylinositol 3-kinase; protein kinase B/Akt; inhibitor; HL-60

Hrčak ID:

67237

URI

https://hrcak.srce.hr/67237

Datum izdavanja:

31.3.2011.

Posjeta: 2.026 *