Mining a human transcriptome database for chemical modulators of NRF2
Fig 5
Examples of dose-, time-, and mutation-dependent modulation of NRF2.
A. Response to 2 μM benzo[a]pyrene from 12 to 72 hours in HepG2 cells. Red circles indicate NRF2 activation, blue circles indicate inactivity. Data from GSE28878, GSE36242, GSE36243, GSE40117. B. Exposure of HepG2 cells to 0.01 μM and 50 μM quercetin from 12 to 48 hours. Data from E-MEXP-2574, GSE28878. C. Exposure of human primary hepatocytes to 10, 50, and 250 μM diazepam from 2 to 24 hours. Data from the TG-GATES study. D. Exposure of lung fibroblasts to dithiothreitol (2.5 mM) at different time points. Data from GSE4301. E. Examples of chemicals suppressing the activation of NRF2 in cancer cells expressing activated PI3K and EGFR. The activating mutations in PI3K3CA (E545K and H1047R) and overexpression of EGFR in the presence of EGF (caEGFR) lead to activation of NRF2 compared to wild-type cells. HCC827 with EGFR Del15 cells possess an amplified EGFR allele with an activating in frame deletion of 15 nucleotides in exon 19. Treatment of the cells with inhibitors for PI3K (LY294002) or EGFR (erlotinib) in the indicated cells suppresses background NRF2 activation.