Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs

doi: 10.1016/j.biopha.2022.112922

Figure Lengend Snippet: Cytotoxicity of SKLB610 in human cell lines overexpressing ABCB1 or ABCG2.

Article Snippet: SKLB610 was obtained from Selleckchem (Houston, TX, USA).

Techniques:

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs

doi: 10.1016/j.biopha.2022.112922

Figure Lengend Snippet: The effect of SKLB610 on ABCB1-mediated multidrug resistance.

Article Snippet: SKLB610 was obtained from Selleckchem (Houston, TX, USA).

Techniques: Concentration Assay

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs

doi: 10.1016/j.biopha.2022.112922

Figure Lengend Snippet: SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cells to anticancer drugs in a concentration-dependent manner. The effect of SKLB610 on ABCG2-mediated resistance to mitoxantrone (A–C), SN-38 (D–F), and topotecan (G–I) was evaluated in the ABCG2-overexpressing human colon cancer cell line S1-MI-80 (A, D and E, left panels) and its drug-sensitive parental line S1 (A, D and E, right panels), ABCG2-overexpressing human NSCLC cell line H460-MX20 (B, E and H, left panels) and its drug-sensitive parental line H460 (B, E and H, right panels), ABCG2-transfected R482-HEK293 cell line (C, F and I, left panels) and the parental line HEK293 (C, F and I, right panels). Cells were treated with increasing concentrations of mitoxantrone, SN-38 or topotecan in the presence of DMSO (empty circles) or SKLB610 at 500 nM (empty squares), 1 μM (filled squares), 2 μM (empty triangles), or 3 μM (filled triangles) for 72 h before analysis as described in Section 2. Points, mean values from at least three independent experiments; bars; S.E.M.

Article Snippet: SKLB610 was obtained from Selleckchem (Houston, TX, USA).

Techniques: Concentration Assay, Transfection

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs

doi: 10.1016/j.biopha.2022.112922

Figure Lengend Snippet: The effect of SKLB610 on ABCG2-mediated multidrug resistance.

Article Snippet: SKLB610 was obtained from Selleckchem (Houston, TX, USA).

Techniques: Concentration Assay

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs

doi: 10.1016/j.biopha.2022.112922

Figure Lengend Snippet: SKLB610 attenuates the drug transport function of ABCG2. The intracellular accumulation of pheophorbide A (PhA), a known fluorescent substrate drug of ABCG2, was determined in (A) S1 and S1-MI-80, (B) H460 and H460-MX20, and (C) pcDNA-HEK293 and R482-HEK293 cells, in the presence of DMSO (control, solid lines), 10 μM SKLB610 (filled solid lines), or 5 μM Ko143, a benchmark inhibitor of ABCG2 (dotted lines). (D) The corresponding quantification of intracellular PhA accumulation in ABCG2-overexpressing S1-MI-80 (black bars), H460-MX20 (white bars) and R482-HEK293 (gray bars). Representative histograms and the quantification values presented as mean ± S.D. calculated from at least three independent experiments are shown. The fluorescence signal was analyzed by flow cytometry as described previously [38].

Article Snippet: SKLB610 was obtained from Selleckchem (Houston, TX, USA).

Techniques: Drug Transport Assay, Control, Fluorescence, Flow Cytometry

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs

doi: 10.1016/j.biopha.2022.112922

Figure Lengend Snippet: SKLB610 has no significant effect on ABCG2 protein expression. The ABCG2-overexpressing S1-MI-80 (A) and H460-MX20 (B) cancer cells were treated with DMSO (vehicle control) or SKLB610 at 0.5 μM, 1 μM, 2 μM, or 3 μM for 72 h and the cell lysates were processed for Western blotting with indicated antibodies as described in Section 2. Representative immunoblots (top) and the corresponding quantification (bottom) of human ABCG2 protein and the internal loading controlα-tubulin are shown. Values are presented as mean ± S.D. calculated from at least three independent experiments.

Article Snippet: SKLB610 was obtained from Selleckchem (Houston, TX, USA).

Techniques: Expressing, Control, Western Blot

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs

doi: 10.1016/j.biopha.2022.112922

Figure Lengend Snippet: SKLB610 enhances drug-induced apoptosis in ABCG2-overexpressing cancer cells. The drug-sensitive human colon cancer cell line S1 and its ABCG2-overexpressing multidrug-resistant subline S1-MI-80 were treated with DMSO (control), 10 μM SKLB610 alone (+ SKLB610), 5 μM topotecan alone (+ topotecan), or a combination of topotecan and SKLB610 (+ topotecan + SKLB610) for 48 h, processed and analyzed by flow cytometry as described in Materials and methods. Representative flow cytometric dot plots are shown (top), and the corresponding quantifications (bottom) are presented as mean ± S.D. calculated from at least three independent experiments. **p < 0.01, versus the same treatment in the absence of SKLB610.

Article Snippet: SKLB610 was obtained from Selleckchem (Houston, TX, USA).

Techniques: Control, Flow Cytometry

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs

doi: 10.1016/j.biopha.2022.112922

Figure Lengend Snippet: SKLB610 stimulates the ATPase activity of ABCG2. The effect of SKLB610 (0–5 μM) on ABCG2-mediated ATP hydrolysis was measured in membrane vesicles prepared from ABCG2 baculovirus-infected High-Five insect cells and recorded as vanadate (Vi)-sensitive ATPase activity as described previously [43]. Points, mean from at least three independent experiments; bars, S.D.

Article Snippet: SKLB610 was obtained from Selleckchem (Houston, TX, USA).

Techniques: Activity Assay, Membrane, Infection

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs

doi: 10.1016/j.biopha.2022.112922

Figure Lengend Snippet: Docking of SKLB610 in the drug-binding pocket of ABCG2. Binding modes of SKLB610 with the protein structure of ABCG2 protein structure (PDB: 6VXH) were predicted by Accelrys Discovery Studio 4.0 software as described in Section 2. SKLB610 (yellow color) is presented in stick representation and the atoms for interacting amino acid residues are colored carbon-gray, hydrogen-light gray, oxygen-red, nitrogen-blue and fluorine-cyan. Proposed interactions are presented as dotted lines.

Article Snippet: SKLB610 was obtained from Selleckchem (Houston, TX, USA).

Techniques: Binding Assay, Software

Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

Article Title: The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs

doi: 10.1016/j.biopha.2022.112922

Figure Lengend Snippet: Simplified schematic illustration of SKLB610 re-sensitizing ABCG2-overexpressing multidrug-resistant cancer cells to cytotoxic anticancer drugs by blocking the drug efflux function of ABCG2. The intracellular concentration of ABCG2 substrate drugs (represented by blue circles) in ABCG2-overexpressing cells is actively reduced by ABCG2-mediated drug transport. In contrast, in the presence of SKLB610 (red triangle), ABCG2-mediated drug efflux is attenuated by SKLB610 outcompeting the binding of ABCG2 substrate drug at the same drug-binding pocket, thus restoring the intracellular accumulation of cytotoxic drugs in ABCG2-overexpressing multidrug-resistant cancer cells.

Article Snippet: SKLB610 was obtained from Selleckchem (Houston, TX, USA).

Techniques: Blocking Assay, Concentration Assay, Drug Transport Assay, Binding Assay

Journal: International Journal of Molecular Sciences

Article Title: Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway

doi: 10.3390/ijms23147853

Figure Lengend Snippet: The IC 50 values of four anticancer agents in human lung cancer cells.

Article Snippet: Anticancer agents, vinorelbine ditartrate (S4269), picropodophyllin (S7668), pacritinib (S8057), and SKLB610 (S6526) were obtained from Selleck Chemicals (Houston, TX, USA).

Techniques:

Journal: International Journal of Molecular Sciences

Article Title: Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway

doi: 10.3390/ijms23147853

Figure Lengend Snippet: CYP27C1-knockdown attenuates anticancer potency of protein kinase inhibitors. ( A – E ) A549-shCYP27C1, H1975-shCYP27C1, and the corresponding control cells were treated with indicated concentration of protein kinase inhibitors (picropodophyllin, pacritinib, and SKLB610). Real-time cell index reflecting cell viability were detected by RTCA-S16 System. Results were analyzed by two-way ANOVA. ****, p <0.0001, **, p <0.01, *, p < 0.05, n.s., p > 0.05. ( F ) Stable CYP27C1-knockdown H1975 cells and the corresponding control cells were treated with indicated concentrations of SKLB610, cell viability was determined by MTS assay at different time point, and analyzed by two-way ANOVA. ****, p <0.0001.

Article Snippet: Anticancer agents, vinorelbine ditartrate (S4269), picropodophyllin (S7668), pacritinib (S8057), and SKLB610 (S6526) were obtained from Selleck Chemicals (Houston, TX, USA).

Techniques: Knockdown, Control, Concentration Assay, MTS Assay