Paracetamol Induces Apoptosis, Reduces Colony Formation, and Increases PTPRO Gene Expression in Human Embryonic Kidney HEK 293 Cells

Abstract

Paracetamol (acetaminophen) is a widely used analgesic and antipyretic drug. Although many studies are available showing that paracetamol causes hepatic damage, few studies exist on renal damage. Protein tyrosine phosphatase receptor type O (PTPRO) protein has tyrosine phosphatase activity and plays a role in the regulation of the renal glomerular pressure/filtration rate relationship in podocyte structure. The PTPRO gene also exhibits characteristics of a candidate tumor suppressor gene. In this study, apoptosis, cell cycle, colony formation, and PTPRO gene expression of the human embryonic kidney (HEK 293) cells were assessed by treating with paracetamol at different concentrations for 24 and 26 h in at least three independent trials. Paracetamol induced dose-dependent apoptosis at all concentrations (5, 10, 15, 20, and 30 mM) for both 24 and 26 h (p < 0.05-p < 0.001). Paracetamol decreased dose-dependent colony-forming potential of cells at 10.000 cells seeding in HEK 293 cells at all concentrations (5, 10, 15, 20, and 30 mM) (p < 0.05-p < 0.001). In HEK 293 cells, paracetamol also increased cell population in the G0-G1 phase at low 5 mM concentration for 26 h (p < 0.05), while reducing cell population in the G2-M phase of the cell cycle at 10 mM and increasing at 30 mM concentration for 24 h (p < 0.05 and p < 0.05, respectively). Paracetamol at high concentration (30 mM) increased PTPRO gene expression in HEK 293 cells for both 24 and 26 h (p < 0.05). In conclusion, our results may indicate that paracetamol may suppress the development of renal cancer by inducing apoptosis and reducing colony formation in a dose-dependent manner, and upregulating PTPRO gene expression in HEK 293 cells at high concentration, in addition to its renal-damaging role. Further research is necessary to determine the potential role or detrimental effects of paracetamol on the development of renal cancer, as the mechanism underlying its effects on renal damage and cancer formation remains unclear.