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. 2020 Dec 14;13(2):e10852. doi: 10.15252/emmm.201910852

Figure 6. MRP1 inhibitor MK‐571 shifts cellular thiol pools, further potentiating APR‐246 efficacy.

Figure 6

  1. Total intracellular glutathione (GSH + GSSG per 106 cells), as determined by GR re‐cycling assay after 24‐h MK‐571 treatment in six different cell lines (n ≥ 3, except HCT116 WT n = 2). *P = 0.014, Paired t‐test. Each dot represents one cell line, see Fig EV6 for individual cell lines and n.
  2. Intracellular oxidized glutathione (GSSG per 106 cells) as shown by LC‐MS in OVCAR‐3 (R248Q TP53) cells at 24‐h treatment with APR‐246 +/− MK‐571 (n = 3).
  3. Intracellular reduced glutathione (GSH per 106 cells) as shown by LC‐MS in OVCAR‐3 cells at 24‐h treatment with APR‐246 +/− MK‐571 (n = 3).
  4. Western blot analysis of MRP1 (Cell Signaling), xCT, and GAPDH of OVCAR‐3 cells treated with APR‐246 +/− MK‐571 for 24 h.
  5. Western blot analysis of MRP1 (Cell Signaling), xCT, and GAPDH of HCT116 WT and R248W cells treated with APR‐246 +/− MK‐571 for 24 h.
  6. Intracellular cystine (CySS per 106 cells) as shown by LC‐MS in OVCAR‐3 cells at 24 h treatment with APR‐246 +/− MK‐571 (n = 3).
  7. Intracellular cysteine (Cys per 106 cells) as shown by LC‐MS in OVCAR‐3 cells at 24 h treatment with APR‐246 +/− MK‐571 (n = 3).

Data information: TP53 status is indicated. Data are represented as mean ± SEM. See also Fig EV6 and Appendix Fig S6.

Source data are available online for this figure.