Study In The Effects Of Phenyhexyle Isothiocyanate (pHI) On PI3K/Akt Signaling Pathway In HL-60Cells

Objects To study the effect of PHI (phenyhexyle isothiocyanate) or/and LY294002oncell growth and apoptosis, and on histone acetylation and PI3K/Akt signaling pathwayin Human promyelocytic leukemia cells (HL-60) in vitro, we further study themechanism of PHI affect in PI3K/Akt signaling pathway.Methods The viability of HL-60cells after treated by indicated concentrations of PHIor/and LY294002was checked by MTT method. Apoptotic cells were measured byFlow cytometry (FCM). The proteins of histone acetylated H3and H4, and the proteinof PI3K/Akt signaling pathway (p-Akt, p-mTOR, p-p70S6K) was detected by WesternBlot.Results (1) The growth of HL-60cells was significantly inhibited in dose and timedependent manner after cultured with PHI or LY294002(P<0.05); FCM displayedthat apoptotic cells were increased after exposure to PHI or LY294002. The effect ofcell growth and apoptotic was stronger after treated by PHI combined with LY294002than that in PHI or LY294002only(P<0.05).(2）PHI induced an accumulation ofhistone acetylated H3and H4, and LY294002has no effect on it. But histoneacetylated H3and H4was slightly upregulated by PHI combined with LY294002thanthat by PHI only.(3)The phosphorylation of Akt (p-Akt), mTOR (p-mTOR),70S6K(p-p70S6K) was decreased after exposure to PHI or LY294002. When PHI combinedwith LY294002, the effect was more stronger (P<0.05).Conclusions PHI or/and LY294002could inhibit the cells growth and induce cellsapoptosis in HL-60cells. PHI induce accumulation of histone acetylated H3and H4,and LY294002has no effect on histone acetylation. PHI and/or LY294002coulddephosphorylate PI3K/Akt pathway. It might be a new agent of anti-leukemia.