ABSTRACT
To investigate the effect of monoamine oxidase inhibitor tranylcypromine (TCP) on the differentiation of human U251 glioma cells, we treated U251 cells with TCP and/or 100 nmol/L histone deacetylase inhibitor trychostatin A (TSA). The differentiation of U251 cells was observed with inverted microscopy. The cell proliferation and cell cycle distribution were determined by MTT assay and flow cytometry, respectively. Apoptosis was observed by Hoechst 33258 staining. The levels of differentiation-related genes were assessed by real-time PCR and Western blotting. TCP-induced differentiation was characterized by typical morphological changes, inhibition of cellular proliferation, accumulation of cells in the G1 phase of the cell cycle, decreased expression of the pluripotency transcription factors Oct4 and Sox2, and increased expression of glial fibrillary acid protein (GFAP). The combination of TCP and TSA treatment also triggered an over-expression of GFAP. These findings suggest that TCP may induce differentiation of U251 glioma cells, and the differentiation process may be promoted by histone deacetylase inhibitor TSA.
Subject(s)
Humans , Brain Neoplasms , Pathology , Cell Line, Tumor , Cell Transformation, Neoplastic , Glioma , Pathology , Histone Deacetylase Inhibitors , Pharmacology , Hydroxamic Acids , Pharmacology , Monoamine Oxidase Inhibitors , Pharmacology , Tranylcypromine , PharmacologyABSTRACT
Objective:To investigate the effect of exogenous nitric oxide(NO) on the growth and proliferation of gastric cancer cell line SGC-7901. Methods:The inhibitory effects of NO donor sodium nitroprusside (SNP) and nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methylester(L-NAME) on the proliferation of SGC-7901 cells were analyzed by MTT assay. The changes of mRNA and protein expression of proliferating cell nuclear antigen(PCNA) and caspase-3 were examined by RT-PCR and Western blotting. The cell cycle was measured using flow cytometry. Results:Compared with control group, more cells in the SNP group were arrested at G_1 and G_0 phases (P<0.05) and fewer cells were at S phases (P<0.05). SNP decreased the speed of cell-cycle progression from G_0/G_1 phase into S phase. SNP inhibited the proliferation of SGC-7901 cells and reduced the mRNA and protein expressions of PCNA and caspase-3. NOS inhibitor L-NAME reversed the effects of SNP. Conclusion:NO inhibited cell growth and proliferation, but accelerated apoptosis of gastric cancer cells.