Fig 2: Representative western blots of ABCC1 levels in various cell lines, including drug-sensitive MCF-7CC12 breast and H69 small cell lung tumour cell lines and their doxorubicin-resistant counterparts (MCF-7DOX2-12 and H69AR cell lines, respectively). ABCC1 levels were also assessed in HEK293 cells and HEK293 cells transfected with an ABCC1 expression vector.

Fig 3: ADSCs support better H37Rv survival and high drug tolerance.a Representative confocal images of GFP-H37Rv-infected ADSCs at 0 h, 3rd, 6th, 9th, and 12th days post infection (dpi), Scale bars, 20 µm. b MFI of GFP-H37Rv/cell across above mentioned time points is represented in bar graph as mean ± SD, n = 3 independent experiments, each representing five fields consisting of 25–100 cells. c Growth kinetics of H37Rv within ADSCs across 12 dpi. d Growth kinetics of H37Rv within human MDMs across 7 days post infection and (e) in THP-1 macrophages across 3 days. f Growth kinetics of BCG within ADSCs and THP-1 macrophages (g) across 0, 1, 2, and 3 dpi. h H37Rv-infected ADSCs were treated with doses of isoniazid (INH), and rifampicin (RIF) for 24 h prior to 3rd, 6th, 9th, and 12th dpi, and were plated for CFU enumeration. n = 3 donors, ****p < 0.0001. i Percent drug-tolerant bacterial population to INH (1 µg/ml) within ADSCs (blue) on 3rd, 6th, 9th, 12th days and within MDMs (purple) on 3rd, 5th, and 7th dpi, respectively (see Methods). n = 3 donors (ADSC), 4 donors (MDM). j Percent drug-tolerant bacterial population to RIF (0.5 µg/ml) within ADSCs (blue) on 3rd, 6th, 9th, and 12th days and within MDMs (purple) on 3rd, 5th, and 7th dpi, respectively. n = 3 donors (ADSC), 4 donors (MDM). k Line histogram of surface and intracellular (I.C.) staining of ABCC1/MRP-1 and ABCG2/BCRP in uninfected and in H37Rv-infected ADSCs, 6 dpi. Numbers represent MFI of individual colored histogram. l Percent INH (1 µg/ml) tolerant bacterial population in ADSCs after knocking down ABCC1 (200 nM siRNA) or ABCG2 (200 nM siRNA) alone or in combination, in H37Rv-infected ADSCs, n = 4 independent experiments. m H37Rv CFU from 6th day infected ADSCs after siRNA mediated knockdown of ABCC1 and ABCG2 for 48 h prior to the time point. n = 4 independent experiments. All data were analyzed by two-tailed unpaired Student’s t test and represented as mean ± SD. Source data are included in the source data file.

Fig 4: Modulation of MRP1 transporter expression in Bx-PC3 cells detected after 4 h exposure and 72 h recovery time. Representative images obtained at immunofluorescence analysis. Original magnification: 10×. (A) Control; (B) sorafenib 10 µg/mL; (C) MK571 1 µg/mL; (D) MK571 1 µg/mL + sorafenib 10 µg/mL; (E) ß-caryophyllene 10 µg/mL; (F) ß-caryophyllene 10 µg/mL + sorafenib 10 µg/mL; (G) ß-caryophyllene oxide 10 µg/mL; (H) ß-caryophyllene oxide 10 µg/mL + sorafenib 10 µg/mL.

Fig 5: MRP1 expression and function are induced in breast cell lines by doxorubicin in vitro. HB2 or T47D cells were treated for 24 h with 1 µM doxorubicin or vehicle control (DMSO). a MRP1 expression was quantified by qPCR (left) or Western blot (right). For qPCR, means with SD of triplicate PCR reactions are presented. Densitometry values are presented beneath MRP1 blots and pertain to the blots presented. Data for qPCR and Western blot are representative of at least 2 independent biological replicates. b Expression of canonical Notch target genes Hes1 and Hey1 was quantified by qPCR. Means are presented with SD of triplicate PCR reactions, and experiments are representative of at least 2 biological repeats. c Efflux of the fluorescent MRP1-substrate, esterified calcein, was assessed using flow-cytometry. Efflux was significantly enhanced in the presence of doxorubicin (non-linear regression T47D p = 0.0035, HB2 p = 0.0009). Analysis of individual timepoints reveal T47D cells show significantly enhanced efflux over 2-5 h post-wash out (two-tailed t-test p < 0.05 at each time point), whilst significant efflux occurred from 4 to 5 h post-wash out for HB2 cells (two-tailed t-test p < 0.01 at 4 h and p < 0.0001 at 5 h). The mean response of 4 independent biological replicates with technical triplicates is presented. Error bars represent the SEM of the 4 replicates