Figure 6 from Targeting the Glucose–Insulin Link in Head and Neck Squamous Cell Carcinoma Induces Cytotoxic Oxidative Stress and Inhibits Cancer Growth

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Auranofin induces cytotoxicity as a pro-oxidant in HNSCC. A and B,In vitro proliferation (top) and intracellular H2O2 levels (bottom) of FaDu (A) or SCC-61 (B) cells treated with vehicle, WZB117 (20 μmol/L), auranofin (1 μmol/L), or combination of WZB117 and auranofin (n = 6 for each group). Two-way ANOVA (top) or two-tailed t test (bottom). ****, P < 0.0001; ***, P < 0.001; **, P < 0.01. C–F,In vivo tumor growth (C), tumor weights (D), images of individual tumors (E), and IHC analysis of GLUT1, pH2A.X, 4HNE, and CC3 (F) in SCC-61 xenograft tumors treated with vehicle PBS/DMSO (n = 6) or auranofin (10 mg/kg i.p. daily; n = 6). Two-way ANOVA for tumor growth (C) and two-tailed t test for tumor weight (D). ****, P < 0.0001; ***, P < 0.001. G, IHC analysis quantification of % area of 4HNE (lipid peroxidation marker), pH2A.X (DNA damage marker), and CC3 (apoptotic cell marker) in xenografted tumors (n = 6 for each group). Four to six images of each tumor were captured and analyzed for quantification. Two-tailed t test. **, P < 0.01. H,In vivo tumor growth of FaDu xenograft tumors treated with vehicle PBS/DMSO (n = 16), WZB117 (20 mg/kg i.p. daily; n = 16), auranofin (10 mg/kg i.p. daily; n = 15), or combination of WZB117 and auranofin (n = 12). Two-way ANOVA. ****, P < 0.0001; ***, P < 0.001; **, P < 0.01. I,In vivo tumor growth of SCC-61 xenograft tumors treated with vehicle PBS/DMSO (n = 6), WZB117 (20 mg/kg i.p. daily; n = 7), auranofin (10 mg/kg i.p. daily; n = 7), or combination of WZB117 and auranofin (n = 7). Two-way ANOVA. ****, P < 0.0001; ***, P < 0.001; **, P < 0.01. All error bars represent mean ± SEM unless otherwise noted. Scale bars, 1 mm. BAY, BAY-876; H&E, hematoxylin and eosin; RLU, relative light unit; WZB, WZB117.

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