Journal: Molecular Cancer Research
Article Title: NAPRT Silencing in FH-Deficient Renal Cell Carcinoma Confers Therapeutic Vulnerabilities via NAD + Depletion
doi: 10.1158/1541-7786.MCR-23-1003
Figure Lengend Snippet: NAPRT loss confers sensitivity to NAMPTis in FH-deficient RCC models. A, Schematic of NAD + biosynthesis pathways, Triple arrow in the de novo synthesis pathway represents five additional enzymatic conversion steps in the pathway. B, YUNK1 cells treated with increasing concentrations of FK866 with or without the addition of 10-μmol/L of NA. C, Total NAD + levels in YUNK1 and YUNK1 shFH cells at baseline and upon treatment with 25-nmol/L FK866 for 24 hours alone or with 10-μmol/L NA. D–F, FH-deficient and NAPRT-silenced NCCFH1 ( D ), UOK262 ( E ), and UOK268 ( F ) cell lines treated with increasing concentrations of FK866 after 8 ( D ), 6 ( E ), or 8 ( F ) days with or without 10-μmol/L NA. G–I, Total NAD + quantification in NCCFH1 ( G ), UOK262 ( H ), and UOK268 ( I ) after 24-hour treatment with 25-nmol/L FK866 alone or with 10-μmol/L NA. Two-way ANOVA, *, P = 0.0151; ****, P ≤ 0.0001. Trp, tryptophan; QA, quinolinic acid; QPRT, Quinolinate phosphoribosyl transferase; NAMN, nicotinic acid mononucleotide; NAPRT, nicotinate phosphoribosyltransferase; NA, nicotinic acid; NMNAT, Nicotinamide mononucleotide adenylyl transferase; NAAD, nicotinic acid adenine dinucleotide; NADS, NAD + synthetase; PARPs, poly(ADP-ribose) polymerases, NAM, nicotinamide; NAMPT, nicotinamide phosphoribosyltransferase; NMN, nicotinamide mononucleotide; NMNAT, nicotinamide mononucleotide adenylyl transferase.
Article Snippet: FK866 (Selleckchem), GNE-617 (Selleckchem), GMX1778 (Selleckchem), olaparib (Selleckchem), and BMN673 (Selleckchem) were dissolved in DMSO and used as indicated.
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