Uptake of high-dose folic acid decreases cell viability and proliferation via JAK/STAT pathway in human prostate cancer cells

Abstract

Aims: Several studies demonstrated that folic acid (FA) supplementation had some effects on prostate cancer initiation. In this study, the effect of FA concentration was evaluated on proliferation and viability in prostate cancer cells (PCCs). Additionally, we also determined the genes dysregulated by the uptake of a certain amount of FA in prostate cancer. Methods: Changes in cell viability and proliferation were analyzed in PCC for low-dose (Group-1; 1 μM, 10 μM, 100 μM) and high-dose (Group-2; 1 mM, 10 mM) FA concentrations by Trypan blue staining and MTT assay, respectively. mRNA expression level of FOLR1, FOLR2 FOLR3, JACK1, STAT3, STAT5/A, STAT5/B, PIAS1, PTPN1, and SOCS1 were determined by quantitative real-time polymerase chain reaction. Results: Cell viability and proliferation were significantly lower than healthy prostate epithelial cells in high-dose FA-treated PCCs. mRNA expressions of FOLR1, JAK1, and STAT3 were significantly upregulated in high-dose FA-treated PCCs compared with the controls. There were no significant alterations in the expression of FOLR2-3, STAT5A/5B, PIAS1, and PTPN1 genes, however, SOCS1 mRNA expression was significantly lower than the controls. Conclusions: Low-dose FA showed no effect on cell viability and proliferation, whereas viability and proliferation were decreased by the uptake of high-dose FA that was supposed to stimulate the mRNA expression of FOLR1 in PCCs. Decreased SOCS1 and increased JAK1 and STAT3 gene expressions implicate the dosage-dependent FA effect on JAK/STAT signaling pathway in prostate cancer.