Fig. 1

Overview of NAD biosynthesis pathway and genetic differences in NAD(H) biosynthesis pathway between CCRF-CEM and MDA MB231 cell lines. a Schematic representation of salvage and de novo pathway of NAD biosynthesis. Pharmacological target of FK866 inhibiting NAMPT is displayed. Abbreviations: NAD, nicotinamide adenine dinucleotide; NA, nicotinic acid; NAMN, nicotinic acid mononucleotide; NAAD, nicotinic acid adenine dinucleotide; NAPRT, nicotinic acid phosphoribosyltransferase; NMNAT, nicotinamide mononucleotide adenylyltransferase; NADS, NAD synthase; NAM, nicotinamide; NMN, nicotinamide mononucleotide; NAMPT, nicotinamide phosphoribosyltransferase; NR, nicotinamide riboside; NRK, nicotinamide riboside kinase; QPRT, quinolinate phosphoribosyltransferase. b, c Expression of NAPRT and QPRT were determined in CCRF-CEM (CEM) and MDA MB231 (MDA) cell lines. d Western blot showing endogenous level of NAPRT, QPRT, and NAMPT in CEM and MDA cell lines. GAPDH was used as a loading control. e, f Sensitivity of CEM and MDA cells to FK866. CEM parental (CEM PA) and FK866-resistant CEM (CEM RES) cells (e) and MDA parental (MDA PA) and FK866-MDA resistant (MDA RES) cells (f) were exposed to various concentrations of FK866 (0.1–100 nM) for 48 h. Percentage of cell viability and EC50 were analyzed by MTT assay. g Downregulation of NAMPT in the resistant cells. Quantitative RT-PCR showing the expression of NAMPT in CEM PA, CEM RES, MDA PA, and MDA RES cells. ACTIN was used as a housekeeping gene