PK11195 can MIT-sensitize MDR cancer cells expressing Pgp, MRP, and/or BCRP. To determine the effects of nontoxic PK11195 (PK) doses on MIT cytotoxicity, DiOC63/PI flow cytometry assays were performed, as described for Figure 1. Cells were incubated with MIT doses that killed substantial fractions of isogenic parental, efflux-deficient cells, including RPMI 8226 (8226), HL60, and ML1 cells, as detailed in individual panel legends. Larger fractions of DOX40 (Pgp-expressing), MR20 (MR20; MRP- and BCRP-expressing), VCR (Pgp-expressing), AR (MRP-expressing), and ML1-BCRP (BCRP-transduced ML1) cells survived 24-hour MIT treatments relative to isogenic parental cells. KG1a (Pgp-expressing) cells were also relatively MIT resistant; 75 μM PK11195 cotreatments substantially decreased surviving fractions in ABC transporter-expressing cells. Summary data from at least 3 assays are shown as means plus or minus SEM.
