Fig. 3: Hypoxanthine potentiates TH9619-induced thymidylate depletion.
From: Formate overflow drives toxic folate trapping in MTHFD1 inhibited cancer cells
a–d, Cell viability dose–response curves of SW620 WT cells treated for 96 h with TH9619 (a), TH9975 (b), MTX (c) or DS18561882 (d), and cultured in RPMI-FBS, RPMI-dFBS or RPMI-dFBS supplemented with 50 μM hypoxanthine, means ± s.d. (n = 8 independent cell cultures for TH9619 and TH9975, n = 4 for MTX and DS18561882). e, Titration of hypoxanthine at indicated doses in SW620 WT cells treated for 96 h with TH9619 (cultured in RPMI-dFBS). Data are displayed as means (n = 2 independent cell cultures). f,g, Dose–response curves of SW620 WT and MTHFD2−/− cells treated for 96 h with TH9619 and cultured in RPMI-FBS (f) or RPMI-dFBS (g), means ± s.d. (n = 3 independent cell cultures). h–k, Cell viability dose–response curves of SW620 WT cells treated for 96 h with TH9619 (h), TH9975 (i), MTX (j) or DS18561882 (k) and 50 μM thymidine, 50 μM hypoxanthine or vehicle (cultured in RPMI-dFBS), means (n = 2 independent cell cultures). l–o, Cell viability dose–response curves of SW620 MTHFD2−/− cells treated for 96 h with TH9619 (l), TH9975 (m), MTX (n) or DS18561882 (o) and 50 μM thymidine, 50 μM hypoxanthine or vehicle (cultured in RPMI-dFBS), means ± s.d. (n = 4 independent cell cultures for TH9619 and TH9975, n = 2 for MTX and DS18561882).
