Study On The Effect Of Monoamine Oxidase Inhibitor Phenelzine On T-lineage Acute Lymphoblastic Leukemia And Its Mechanism

Objective: To investigate the effect of monoamine oxidase inhibitor phenelzineon cell proliferation and apoptosis and epigenetic change in acute lymphoblasticleukemia, Molt-4cells line in vitro, we study its potential mechanism.Methods：⑴T he viability of Molt-4cells after exposure to Phenelzine wasdetected by MTT. Apoptotic rate was measured by flow cytometry.⑵The variationof apoptosis associated protein Caspase-3, Bcl-2, Bax, cyclin-dependent kinaseinhibitor p21, tumor suppressor protein p15, and the expression level of histonemethylation of H3K4, H3K9and histone acetylation of H3, DNMT1was detected byWestern Blot.Results:(1) Phenelzine inhibited Molt-4cell proliferation in (87.68±3.54)%,(67.84±3.24)%,(51.48±3.37)%,(28.72±2.56)%respectively after exposured tophenelzine in5μmol/L,10μmol/L,15μmol/L,20μmol/L for24h, p<0.05. After10μ mol/L of phenelzine exposure for24,48,72h, cell proliferation rate was (67.84±3.24)%,(50.24±2.01)%,(40.31±2.25)%, p<0.05.(2) Phenelzine promoted cellapoptosis. The apoptotic rate was (13.64±2.58)%,(31.24±3.42)%,(56.37±4.26)%after treated phenelzine in5μ mol/L,10μ mol/L,20μ mol/L for24h, which was inconcentration dependent. Phenelzine increased the apoptosis associated protein Bax,apoptosis executioner Caspase-3, p21, while decreased antiapoptotic protein Bcl-2.(3)Phenelzine upregulated histone H3k4me1, H3K4me2and histone acetylated H3.Alteration of histone H3k4me3, H3K9me1, H3K9me2was not seen.(4) Phenelzineinhibite DNMT1and increased protein P15.Conclusions:(1)The monoamine oxidase inhibitor phenelzine, which is LSD1inhibitor, inhibit Molt-4cell proliferation. It might related to phenelzine decrease P21,which is cyclin-dependent kinase inhibitor.(2)Phenelzine promote cell apoptosis, which might be consqence of its downregulation of Bcl-2, upregulation of Bax,caspase-3.(3)Phenelzine improved histone H3K4me1, H3K4me2and histoneacetylation H3, which involved in gene transcriptional activation.(4)Phenelzinedownregulate the DNA demethylase, DNMT1, induce P15gene demethylation andP15protein was de novo.