psc833 valspodar  (Tocris)

Journal: Cancers

Article Title: A Role for iNOS in Erastin Mediated Reduction of P-Glycoprotein Transport Activity

doi: 10.3390/cancers16091733

Figure Lengend Snippet: Changes in P-glycoprotein (P-gp) transport activity in brain capillaries ( N = 15–20 per data point) from six rats treated with erastin. ( A ) Representative confocal fluorescent and DIC images of brain capillaries after a 60-min incubation with 2.0 μM NBD-CSA; note the high luminal fluorescence in the control capillary and ( B ) decreased luminal fluorescence in capillaries exposed to 10.0 μM PSC833 (Scale bars, 10 μm). Representative confocal images of the luminal fluorescence (LF) from ( C ) male and female brain capillaries associated with P-glycoprotein (P-gp) transport activity at increasing doses of erastin in brain capillaries of SD rats. Bar graphs of P-glycoprotein transport activity determined by LF in ( D ) male and ( E ) female capillaries. Graphs of LF measuring P-glycoprotein (P-gp) transport activity in male ( F ) and female ( G ) capillaries (capillary N = 15–20 per experimental data point) exposed to 0.001 μM erastin over time. Dotted red line denotes multiple comparison. Significance is as compared to control unless otherwise specified: * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: PSC833 (valspodar), the P-glycoprotein-specific inhibitor, was purchased from Tocris Bioscience.

Techniques: Activity Assay, Incubation, Fluorescence, Control, Comparison

Journal: Fluids and Barriers of the CNS

Article Title: Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses

doi: 10.1186/s12987-022-00344-w

Figure Lengend Snippet: Protein levels of transporters and receptor in hCMEC/D3 cells cultured either in static or under shear stress exposure of 5 or 10 dyn.cm −2 . Data are presented as means \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pm$$\end{document} ± standard deviation ( a ) Label free quantification (n = 4 to 5) ( b ) Targeted proteomic analysis of ABC transporters from two independent experiments in triplicates. Expression ratio are normalized with the corresponding value in static. c Functionality of P-gp and MRP transporters. Calcein-AM or DCFDA were respectively incubated for 30 min with or without specific inhibitor (respectively Valspodar or MK-571). Histograms present the cellular uptake of fluorescent metabolites of substrates normalized with the value static condition without inhibitor. Three independent experiments were performed in triplicate. Statistical significance was determined by ANOVA followed by a Tukey’s test (*p < 0.05; **p < 0.01; ***p < 0.001)

Article Snippet: Valspodar (PSC833, Sigma-Aldrich) and MK-571 (Sigma-Aldrich) were used as potent inhibitors of P-gp and MRPs transporters, respectively [ , ].

Techniques: Cell Culture, Standard Deviation, Expressing, Incubation

Journal: Acta Pharmaceutica Sinica. B

Article Title: Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

doi: 10.1016/j.apsb.2020.12.021

Figure Lengend Snippet: Type II POPs but not type I POPs overcome ATP binding cassette subfamily B member 1 (ABCB1)-mediated multidrug resistance (MDR) of paclitaxel and doxorubicin in MDA435/LCC6 MDR1 cells. Cytotoxicity of paclitaxel (A)–(C) and doxorubicin (Dox) (D)–(F) in MDA435/LCC6 and ABCB1-transfected MDA435/LCC6 MDR1 cells in the absence or presence of PSC833, P1 , or P4 . Effect of type II POPs ( P4, P5 , or P6 ) on paclitaxel-induced cell cycle arrest in MDA435/LCC6 (G) and MDA435/LCC6 MDR1 (H) cells, and on paclitaxel-induced apoptosis in MDA435/LCC6 (I) and MDA435/LCC6 MDR1 (J) cells. All data are expressed as mean ± SD ( n = 3). ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001, compared to the corresponding subgroups in control group; # P < 0.05, ## P < 0.01, ### P < 0.001, compared to the corresponding subgroups in paclitaxel alone group, by two-way ANOVA test followed by Tukey post hoc test.

Article Snippet: PSC833 (valspodar) was provided by Novartis (East Hanover, NJ, USA).

Techniques: Binding Assay, Transfection, Control

Journal: Acta Pharmaceutica Sinica. B

Article Title: Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

doi: 10.1016/j.apsb.2020.12.021

Figure Lengend Snippet: Reversal effect of type II POPs ( P4 , P5 , and P6 ) on ABCB1-mediated paclitaxel or doxorubicin MDR in MDA435/LCC6 MDR1 resistant cells.

Article Snippet: PSC833 (valspodar) was provided by Novartis (East Hanover, NJ, USA).

Techniques:

Journal: Acta Pharmaceutica Sinica. B

Article Title: Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

doi: 10.1016/j.apsb.2020.12.021

Figure Lengend Snippet: Mechanisms of ABCB1 inhibition by type II POPs. Representative flow cytometry histogram and fluorescence retention in MDA435/LCC6 MDR1 (A) and MDA435/LCC6 (B) cells incubated with ABCB1 substrate Rh123 in the absence or presence of individual POPs or positive controls (verapamil and PSC833) for 30 min plus a 1-h substrate-free efflux. ∗∗ P < 0.01, ∗∗∗ P < 0.001, compared to Rh123 alone group, by one-way ANOVA test followed by Tukey post hoc test. (C) Protein expression of ABCB1 in SW620 Ad300 cells treated with individual POPs. (D) Effects of individual POPs, verapamil, and PSC833 on ATPase activity of human recombinant ABCB1. ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001, compared to vehicle control, by one-way ANOVA test followed by Tukey post hoc test. (E) Relative shift of the mouse monoclonal ABCB1 antibody (UIC-2) in MDA435/LCC6 MDR1 cells treated with individual POPs. The results are presented as % UIC-2 shift (relative to IgG2b fluorescence signal) normalized to the signal of PSC833 (set as 100%). ∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001, compared to oxaliplatin group, by two-way ANOVA test followed by Tukey post hoc test. (F) Molecular docking of type II POPs ( P4 , P5 , and P6 ) to both inactive and active state of human ABCB1. Tariquidar, an ABCB1 inhibitor known to activate ABCB1, was also docked for a comparison. All data are expressed as mean ± SD ( n = 3). FITC, fluorescein isothiocyanate.

Article Snippet: PSC833 (valspodar) was provided by Novartis (East Hanover, NJ, USA).

Techniques: Inhibition, Flow Cytometry, Fluorescence, Incubation, Expressing, Activity Assay, Recombinant, Control, Comparison

Journal: Acta Pharmaceutica Sinica. B

Article Title: Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo

doi: 10.1016/j.apsb.2020.12.021

Figure Lengend Snippet: Comparison of type II POPs with known ABCB1 inhibitors.

Article Snippet: PSC833 (valspodar) was provided by Novartis (East Hanover, NJ, USA).

Techniques: Comparison, Drug discovery, Activity Assay, Expressing, Binding Assay