c-MET inhibition disrupts antioxidant mechanism in hypoxia. (A) Percentage of NNI-24 (top) and NNI-11 (bottom) cell population with high intracellular ROS (CellROXHi) when treated with crizotinib (500 nM), foretinib (500 nM), and tivantinib (1000 nM) for 0, 12, 24, and 48 h in normoxia and hypoxia. (B) Relative mRNA expression of antioxidant genes in NNI-24 and NNI-11 treated as described in (A) for 0, 12, 24, and 48 h in hypoxia. Rpl27 was used as the endogenous reference gene. Data are represented as mean±SD from n = 3 replicates. * p < 0.05, ** p < 0.01, *** p < 0.001 compared to other groups. (C) Cell viability of NNI-24 and NNI-11 treated as described in (A), in the presence or absence of N-acetyl cysteine (NAC) in normoxia and hypoxia. NAC was used at 500 and 2000 µM. Data are represented as mean±SD from n = 3 replicates. * p < 0.05, ** p < 0.01, *** p < 0.001, N.S. denotes non-significant.