The Combination of Mannose with Metformin and Orlistat Synergistically Induces Apoptosis and Suppresses GFAT1 and <i>PD-1</i> Gene Expression in a Lymphoid Cell Line (NALM-6)

Abstract

Background: The beneficial effects of mannose, metformin, and orlistat in inhibiting cancer cells have been reported previously. Objectives: A study was conducted here to investigate their impact on Nalm-6 lymphoid cell survival and apoptosis separately and in combination. Methods: The nalm-6 cells were meticulously cultured in RPMI1640 medium. The IC50 of drugs was calculated using the MTT method. Cells were incubated with the examined concentrations of drugs for 48 hours in a 96-well plate. The expression of PD-1 and glutamine-fructose amidotransferase (GFAT1) genes was evaluated using real-time PCR based on the SYBR Green® method. Apoptosis was detected by staining cells with DAPI and observing them through fluorescent microscopy. The groups were compared using ANOVA and Tukey post hoc test, ensuring the robustness of the results. Results: Separate and concomitant treatment with metformin, mannose, and orlistat was associated with reduced survival, improved apoptosis, and decreased expression of PD-1 and GFAT1 in the Nalm-6 cell line. Meanwhile, the concomitant use of mannose plus metformin and mannose plus orlistat had beneficial synergistic effects on the survival of the studied cells. Conclusions: Treatment of Nalm-6 cells with the studied compounds was associated with beneficial effects on inhibiting these cells.