β-Alanine mediated inhibition of PTHR1suppresses the proliferation, invasion and tumorigenesis in metastatic human osteosarcoma U2OS cells

Abstract

The present study was aimed to investigate the effect of β-alanine mediated inhibition of parathyroid hormone 1 receptor (PTHR1), suppresses the proliferation, invasion, and tumorigenesis in metastatic human osteosarcoma U2OS cells. Cell survival rate was reduced 96.54, 91.23, 84.62, 76.42 and 69.72% following incubation of β-alanine at 50–250 mM respectively. Annexin-V/propidium iodide (PI) staining showed a reduced level of viable cells (71.37%) at 250 mM of β-alanine. U2OS cell proliferation, adhesion, invasion, and migration were decreased following incubation with β-alanine. Matrix metalloproteinases-2/9 (MMP-2/9) mRNA expression was reduced, whereas tissue inhibitors of metalloproteinases-1/2 (TIMP-1/2) mRNA expression was increased remarkably. The mRNA and protein of PTHR1 were reduced in the cells following incubation with β-alanine. Vacuole membrane protein 1 (Vmp1) mRNA and protein were increased in the cells following incubation with β-alanine. In tunel assay, the number of PTHR1 positive cells was 67, 34 and 17 following incubation with β-alanine at 150, 200 and 250 mM respectively. Taking all these data together, it is concluded that β-alanine mediated inhibition of PTHR1 reduced the U2OS cell proliferation, invasion, migration, and tumorigenesis. Furthermore, the results indicated that the β-alanine induced expression of PTHR1 has a positive relationship with invasion and metastasis of osteosarcoma cells.