FIG. 7.
Effect of nuclear NRF-2 level on the cell toxicity and oxidative stress induced by PL and PEITC. Three model tumor cell lines, p53fl/Kras G12D, p53fl/Kras G12D/Nrf-2−, p53fl/Kras G12D/Keap-1− were created to provide a range of nuclear NRF-2 levels based on specific mutations found in A549 cells. (A,B) The p53fl/Kras G12D and the knockout cell lines treated with PL or PEITC concentrations from 0 to 15 μM. Number of live cells remaining on the dish after 48 h were counted and compared to a DMSO-only control after 48 h. The Keap-1 null cell lines were the most resistant to both compounds. Each point of the growth curve represents mean ±95% confidence interval from three biological replicates and two technical replicates each. (C) Representative blot measuring Prx-2 oxidation via treatment by 10 μM PL for a period of 10 h. The Keap-1 null cell line showed the least amount of oxidation in response to PL treatment, and subsequently, it is the most resistant to the drug. (D) Densitometry data for the fold change in oxidized Prx-2 over DMSO control in NRF-2 cells treated with PL. The bar graph represents mean ± standard deviation from two biological replicates performed. *p < 0.05, **p < 0.01.