Figure 5.
Candidate drugs cause oxidative stress in OC spheroids. (A) Ovcar8 cells grown in TIC-enriching spheroid conditions have significantly higher levels of ROS compared to adherent Ovcar8. (B) Ovcar8 spheroids treated with the drugs at LD50 for 6h showed elesclomol produced higher levels of intracellular ROS compared to vehicle. (C) Ovcar8 spheroids treated with LD50 concentrations of the drugs were analyzed for MitoSOX levels. Bardoxolone methyl and salinomycin for 6 h showed increased MitoSOX compared to control. (D) Representative images of Nrf2 (red) translocation to the nucleus (blue, DAPI) in OV90 spheroids after 6h treatment with each of the drugs at respective LD50 doses. 63X objective, scale bar is 10μm. (E) Quantification of Nrf2 nuclear localization in each cell line treated with each of the drugs for 6h. Graphs represent mean and SEM compared to control ** p < 0.01, *** p < 0.001.