Elacridar

Belinostat (PXD101) and elacridar were purchased from MedChemExpress, USA. These agents were dissolved in DMSO to 100 mM and stored at −20 °C. Before treatment, the stock solution is diluted to different concentrations. The final concentration of DMSO in cultures is 0.1% (v/v) or less. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) was obtained from Sigma, USA. The primary antibodies against OAZ1 and P-gp were obtained from Abcam (Cambridge, MA). The primary antibodies against acetylated Histone 4(Ac-H4) were purchased from Millipore, USA. The primary antibodies against HDAC1, Histone 4, p21, and β-actin were obtained from Cell Signaling Technology (Danvers, MA). The OAZ1 Silencer Select Validated siRNA was obtained from Life Technologies, USA.

3-(4,5-dimethylthiazol-2-yl)-2 and 5-diphenylte trazolium bromide (MTT) were purchased from Gen-View Scientific Inc. (Calimesa, CA, USA). Flavonoids were purchased from Aladdin Chemistry Co., Ltd. (Shanghai, China) (purity > 98%). Elacridar was purchased from MedChemExpress. (New Jersey, USA) (purity > 98%) (CAS: 143664-11-3) and used as an inhibitor of P-gp. Daunorubicin hydrochloride was purchased from Tokyo Chemical Industry Co. Ltd. (Tokyo, Japan) (purity > 98%) (CAS:23541-50-6) and used as a substrate of P-gp. All the compounds were dissolved and diluted to a final concentration of 0.1% (v/v) DMSO. Fetal bovine serum (FBS) was obtained from Zhejiang Tianhang Biotechnology Co.,Ltd. (Zhejiang, China). Dulbecco’s modified essential medium (DMEM) was purchased from Hyclone (Logan, UT, USA). The 96-well plates were purchased from Corning Costar (Cambridge, MA, USA).

^99mTc MIBI (Cardiolite; Fujifilm RI Pharma., Co., Ltd., Tokyo, Japan) and doxorubicin (Adriamycin; Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan) were used as tracers. A stock solution of ^99mTc MIBI was prepared by mixing 10 MBq of ^99mTc MIBI with 2 mL of saline solution; this solution was then used in the in vitro and in vivo experiments [10 (link),11 (link)]. A stock solution of doxorubicin was prepared by mixing 1 mg of doxorubicin with 1 mL of saline solution. This solution was then used in the in vivo experiment. A stock solution of MDR modulator was prepared from an acridone carboxamide derivative, GG918, (N-{4-(2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl)-phenyl}-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide; Elacridar; MedChem Express, LLC, Monmouth Junction, NJ, USA) [7 (link),12 (link)].

5-Fluorouracil (5-FU) (Sigma Aldrich, Milan, Italy) was used at different concentrations and for different time points based on the specific experiment. Recombinant human IFN-β and IFN-γ (Peprotech, Tebu-Bio, Milan, Italy) were used at different concentrations and for different time points based on the experiment. Navitoclax and Elacridar were obtained from MedChemExpress (D.B.A., Milan, Italy) and Selleckchem (Aurogene, Rome, Italy), respectively. Radiation treatment was performed using the Elekta Precise Linear Accelerator (Elekta Oncology Systems, Crawley, UK) for different doses and time points.

CBD, CBDA, CBDV, CBG, CBGA, Δ⁹-THC and Δ⁹-THCA were purchased from THC Pharm GmbH (Frankfurt, GER). CBGA was also purchased from Cayman Chemical (Ann Arbor, USA). CBDA was also generously provided by Medropharm GmbH (Schönenberg, CHE). CBDVA was synthesized by Professor Michael Kassiou at the University of Sydney. Elacridar, digoxin and loratadine were purchased from MedChem Express LLC (Princeton, USA). Prazosin and Lucifer Yellow CH dipotassium salt were purchased from Sigma-Aldrich (St. Louis, USA). The full-spectrum cannabis extract was purchased from Ecofibre (Brisbane, AUS) with its cannabinoid content presented in Supplemental Table 1. Terpene content of the full-spectrum extract in percent content (w/w) is as follows: β-caryophyllene, 0.525; β-linalool, 0.011; D-limonene, 0.006 and β-pinene, 0.004.