Synergistic effects of phenylhexyl isothiocyanate and LY294002 on the PI3K/Akt signaling pathway in HL-60 cells

摘要

The aim of the present study was to investigate the synergistic effect of phenylhexyl isothiocyanate (PHI) and LY294002 [an inhibitor of phosphoinositide 3-kinase (PI3K)] on the PI3K/protein kinase B (Akt) signaling pathway, modulating histone acetylation, inhibiting cell viability and inducing apoptosis in HL-60 cells. The inhibition of HL-60 cell viability was monitored using an MTT assay. Cell apoptosis was measured using flow cytometry. Expression of acetylated histone H3 and histone H4, and the Akt signaling pathway proteins phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR) and phosphorylated ribosomal protein S6 kinase (p-p7056x) was detected using western blotting. The results of the present study identified that PHI and LY294002 were able to inhibit cell viability and induce cell apoptosis in HL-60 cells. The combination exhibited a synergistic effect on cell viability and apoptosis. PHI treatment led to an accumulation of acetylated histone H3 and histone H4, but LY294002 treatment had no effect on histone acetylation. However, LY294002 was identified to enhance the effect of PHI on histone acetylation in HL-60 cells. PHI and/or LY294002 were identified to dephosphorylate proteins in the PI3K/Akt signaling pathway, with a synergistic effect observed when used in combination. The results of the present study indicated that the combination of PHI and LY294002 may offer a novel therapeutic strategy for acute myeloid leukemia.