Study On The Effect Of Monoamine Oxidase Inhibitor Phenelzine On Histone Methylation And Wnt Signal Pathway In Mantle Cell Lymphoma

Objective: To investigate the effect of monoamine oxidase inhibitor phenelzine,which is LSD1inhibitor,on cell proliferation and apoptosis, histone methylation ofH3K4and histone acetylation of H3, and Wnt signal pathway in mantle celllymphoma Jeko-1cells line in vitro. We further study its potential mechanisms.Methods：(1)The viability of Jeko-1cell after exposure to phenelzine was checked byMTT method. Apoptotic rate was measured by flow cytometry.(2)The variation ofapoptosis associated protein Caspase-3, Bcl-2, Bax and p21protein, the expression ofmono-or dimethylated, trimethylated of H3K4and histone acetylation of H3and theprotein of Wnt signal pathway was detected by Western Blot.Results:(1) Phenelzine inhibited Jeko-1cell proliferation in (10.43±1.85)%,(36.54±4.34)%,(43.52±3.37)%,(80.05±3.56)%respectively after exposured tophenelzine in5μmol/L,10μmol/L,15μmol/L,20μmol/L for24h, p<0.05.(2) Phenelzinepromoted cell apoptosis.The apoptotic rate was (3.64±1.52)%,(17.64±3.46)%,(30.14±3.16)%,(52.45±5.31)%after treated phenelzine in0μmol/L,5μmol/L,10μmol/L,20μmol/L for24h, which was in concentration dependent. Phenelzine increasedthe apoptosis associated protein Bax, apoptosis executioner Caspase-3, p21, whiledecreased antiapoptotic protein Bcl-2.(3) Phenelzine upregulated histone H3K4me1,H3K4me2and histone acetylated H3. Alteration of histone H3K4me3was not seen.(4)Phosphorylation ofGSK-3β,β-catenin, c-myc, cyclinD1was decreased after exposureto phenelzine for24hours.Conclusions:(1) The monoamine oxidase inhibitor phenelzine inhibits Jeko-1cellproliferation,which might result of phenelzine decreasing P21, one ofcyclin-dependent kinase inhibitor.(2)Phenelzine downregulate Bcl-2, upregulate Bax, caspase-3, and promote cell apoptosis.(3)Phenelzine improved histone H3K4me1,H3K4me2and histone acetylation H3, but it do not effect on histone H3K4me3.(4)Phenelzine phosphorlate Wnt/β-catenin signal pathway, may have somerelationship with the histone methylation.