Journal: Bioinformation

Article Title: Molecular modeling of NK-CT1, from Indian monocellate cobra (Naja kaouthia) and its docking interaction with human DNA topoisomerase II alpha

doi: 10.6026/97320630012105

Figure Lengend Snippet: Docked structure of NK-CT1 with DNA Topoisomerase II alpha. Figure was generated in the GUI of AUTODOCK MGL Tools. Docked structure showing the protein NK-CT1 (in ball and stick model) with DNA Topoisomerase II alpha (marked as blue arrow) complexes with oligo-nucleotide (PDB ID: 4FM9) shown in Panel A (marked as white circle). Interaction of NK-CT1 (Panel B marked with white circle) with the DNA Topoisomerase II alpha showed that some specific residues are interacting with the oligo-nucleotide bound to the protein and therefore can be predicted that NK-CT1 interacts with the DNA binding domain of Topoisomerase II alpha.

Article Snippet: The docked conformations that were generated after docking were selected based on their binding energy and corresponding figure was developed from Graphics User Interface of AUTODOCK MGL Tools.

Techniques: Generated, Binding Assay

Journal: Cancer letters

Article Title: The FLT3 inhibitor midostaurin selectively resensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic agents

doi: 10.1016/j.canlet.2019.01.001

Figure Lengend Snippet: Drug-sensitive parental pcDNA-HEK293 cells (A - C, left panels), ABCB1-transfected MDR19-HEK293 cells (A, right panel), ABCC1-transfected MRP1-HEK293 cells (B, right panel), ABCG2-transfected R482-HEK293 cells (C, right panel), human KB-3–1 epidermal cancer cells (D, left panel), ABCB1-overexpressing variant KB-V1 cancer cells (D, right panel), human OVCAR-8 ovarian cancer cells (E, left panel) and ABCB1-overexpressing variant NCI-ADR-RES cancer cells (E, right panel), were treated with calcein-AM, a known fluorescent substrate of ABCB1 and ABCC1, or PhA, a known fluorescent substrate of ABCG2, in the presence of DMSO (control, solid lines), or 10 μM midostaurin (shaded, solid lines), or 20 μM of ABCB1 reference inhibitor verapamil (A, D and E, dotted lines), or 25 μM of ABCC1 reference inhibitor MK-571 (B, dotted lines), or 1 μM of ABCG2 reference inhibitor Ko143 (C, dotted lines) as indicated. The intracellular accumulation of the respective fluorescent substrate in each cell line was analyzed immediately by flow cytometry as described previously [38]. Representative histograms of three independent experiments and immunoblots of total cell expression of ABCB1 (A, D and E, inset) or ABCC1 (B, inset) or ABCG2 (C, inset) in total cell lysate protein (10 μg/lane) from pcDNA-HEK293, MDR19-HEK293, MRP1-HEK293, R482- HEK293, KB-3–1, KB-V-1, OVCAR-8 and NCI-ADR-RES cells are shown.

Article Snippet: Collectively, our results indicate that midostaurin interacts at the drug-binding pocket of ABCB1 and inhibits the activity of ABCB1. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 caption a8 Docking of midostaurin in the drug-binding pocket of ABCB1. (A) The homology model of ABCB1, based on the PDB:5KPI mouse P-glycoprotein structure, was used for exhaustive docking using AutoDock Vina software.

Techniques: Transfection, Variant Assay, Control, Flow Cytometry, Western Blot, Expressing

Journal: Cancer letters

Article Title: The FLT3 inhibitor midostaurin selectively resensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic agents

doi: 10.1016/j.canlet.2019.01.001

Figure Lengend Snippet: Parental HEK293 cells (A - C, left panels), MDR19-HEK293 cells (A, right panel), MRP1-HEK293 cells (B, right panel) and R482-HEK293 cells (C, right panel) were treated with increasing concentrations of ABCB1 substrate chemotherapy drug paclitaxel, ABCC1 substrate chemotherapy drug etoposide, or ABCG2 substrate chemotherapy drug SN-38, respectively, in the presence of DMSO (open circles), or midostaurin at 20 nM (open squares) or at 50 nM (filled squares), or a reference inhibitor as a positive control (filled circles). (D) Drug-sensitive parental KB-3–1 cancer cells (left panel) and ABCB1-overexpressing variant KB-V1 cancer cells (right panel), (E) drug-sensitive parental OVCAR-8 cancer cells (left panel) and ABCB1-over-expressing variant NCI-ADR-RES cancer cells (right panel) were treated with paclitaxel in the presence of DMSO (open circles), or midostaurin at 50 nM (open squares) or at 100 nM (filled squares) or at 200 nM (open triangles). Points, mean values from at least three independent experiments; bars; S.E.M.

Article Snippet: Collectively, our results indicate that midostaurin interacts at the drug-binding pocket of ABCB1 and inhibits the activity of ABCB1. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 caption a8 Docking of midostaurin in the drug-binding pocket of ABCB1. (A) The homology model of ABCB1, based on the PDB:5KPI mouse P-glycoprotein structure, was used for exhaustive docking using AutoDock Vina software.

Techniques: Positive Control, Variant Assay, Expressing

Journal: Cancer letters

Article Title: The FLT3 inhibitor midostaurin selectively resensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic agents

doi: 10.1016/j.canlet.2019.01.001

Figure Lengend Snippet: Chemosensitization effect of midostaurin on drug resistance mediated by ABCB1, ABCC1 or ABCG2 in HEK293 cells.

Article Snippet: Collectively, our results indicate that midostaurin interacts at the drug-binding pocket of ABCB1 and inhibits the activity of ABCB1. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 caption a8 Docking of midostaurin in the drug-binding pocket of ABCB1. (A) The homology model of ABCB1, based on the PDB:5KPI mouse P-glycoprotein structure, was used for exhaustive docking using AutoDock Vina software.

Techniques: Concentration Assay

Journal: Cancer letters

Article Title: The FLT3 inhibitor midostaurin selectively resensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic agents

doi: 10.1016/j.canlet.2019.01.001

Figure Lengend Snippet: (A) Human KB-3–1 epidermal cancer cells and ABCB1-overexpressing variant KB-V1 cancer cells, as well as (B) human OVCAR-8 ovarian cancer cells and ABCB1-overexpressing variant NCI-ADR-RES cancer cells were treated with DMSO or midostaurin at various concentrations (50 nM, 100 nM and 200 nM) for 72 h before processed for immunoblotting and quantification as described previously [38]. α-Tubulin was used as an internal loading control. Values are presented as mean ± S.D. calculated from three independent experiments.

Article Snippet: Collectively, our results indicate that midostaurin interacts at the drug-binding pocket of ABCB1 and inhibits the activity of ABCB1. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 caption a8 Docking of midostaurin in the drug-binding pocket of ABCB1. (A) The homology model of ABCB1, based on the PDB:5KPI mouse P-glycoprotein structure, was used for exhaustive docking using AutoDock Vina software.

Techniques: Variant Assay, Western Blot, Control

Journal: Cancer letters

Article Title: The FLT3 inhibitor midostaurin selectively resensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic agents

doi: 10.1016/j.canlet.2019.01.001

Figure Lengend Snippet: The effect of midostaurin on colchicine-induced apoptosis was determined in drug-sensitive parental human KB-3–1 cancer cells (top panels) and ABCB1-overexpressing KB-V1 cells (lower panels). Cells were treated with either DMSO (control), 500 nM colchicine (+colchicine) or a combination of 500 nM colchicine and 200 nM of midostaurin (+colchi-cine + midostaurin) for 48 h, isolated and analyzed by flow cytometry as described previously [27]. The dot plots of representative experiments are shown. (B) Quantification of colchicine-induced apoptosis in KB 3–1 and KB-V1 cancer cells. The early apoptosis and late apoptosis/necrosis data are given as mean values ± S.D. calculated from at least three independent experiments. *P < 0.05; **P < 0.01; ***P < 0.001.

Article Snippet: Collectively, our results indicate that midostaurin interacts at the drug-binding pocket of ABCB1 and inhibits the activity of ABCB1. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 caption a8 Docking of midostaurin in the drug-binding pocket of ABCB1. (A) The homology model of ABCB1, based on the PDB:5KPI mouse P-glycoprotein structure, was used for exhaustive docking using AutoDock Vina software.

Techniques: Control, Isolation, Flow Cytometry

Journal: Cancer letters

Article Title: The FLT3 inhibitor midostaurin selectively resensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic agents

doi: 10.1016/j.canlet.2019.01.001

Figure Lengend Snippet: The effect of midostaurin at indicated concentrations ranging from 0 to 200 μM on vanadate-sensitive ABCB1 ATP hydrolysis was determined by endpoint Pi liberation assays as described in the Methods section. Data are presented as mean ± S.D. from three independent experiments.

Article Snippet: Collectively, our results indicate that midostaurin interacts at the drug-binding pocket of ABCB1 and inhibits the activity of ABCB1. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 caption a8 Docking of midostaurin in the drug-binding pocket of ABCB1. (A) The homology model of ABCB1, based on the PDB:5KPI mouse P-glycoprotein structure, was used for exhaustive docking using AutoDock Vina software.

Techniques:

Journal: Cancer letters

Article Title: The FLT3 inhibitor midostaurin selectively resensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic agents

doi: 10.1016/j.canlet.2019.01.001

Figure Lengend Snippet: (A) The homology model of ABCB1, based on the PDB:5KPI mouse P-glycoprotein structure, was used for exhaustive docking using AutoDock Vina software. The receptor grid was centered at x = 20, y = 60 and z = 5 Å, and 33 residues in the binding-pocket were set as flexible. The box size was 50 × 50 × 50 Å and the exhaustiveness was set at 100. The first nine poses with the highest docking scores are shown in red sticks. For the purpose of clarity, only transmembrane helices 1 and 4 to 8 are presented in grey as a cartoon representation. The figure was prepared using PyMOL software. (B) The lowest docking score pose binding mode of midostaurin is presented in red sticks. Residues within 4 Å distance of midostaurin are shown in grey. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Article Snippet: Collectively, our results indicate that midostaurin interacts at the drug-binding pocket of ABCB1 and inhibits the activity of ABCB1. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 caption a8 Docking of midostaurin in the drug-binding pocket of ABCB1. (A) The homology model of ABCB1, based on the PDB:5KPI mouse P-glycoprotein structure, was used for exhaustive docking using AutoDock Vina software.

Techniques: Software, Binding Assay

Journal: Cancer letters

Article Title: The FLT3 inhibitor midostaurin selectively resensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic agents

doi: 10.1016/j.canlet.2019.01.001

Figure Lengend Snippet: Sensitivity of ABCBl-expressing cells and their respective drug-sensitive parental cells to midostaurin.

Article Snippet: Collectively, our results indicate that midostaurin interacts at the drug-binding pocket of ABCB1 and inhibits the activity of ABCB1. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 caption a8 Docking of midostaurin in the drug-binding pocket of ABCB1. (A) The homology model of ABCB1, based on the PDB:5KPI mouse P-glycoprotein structure, was used for exhaustive docking using AutoDock Vina software.

Techniques:

Journal: Cancer letters

Article Title: The FLT3 inhibitor midostaurin selectively resensitizes ABCB1-overexpressing multidrug-resistant cancer cells to conventional chemotherapeutic agents

doi: 10.1016/j.canlet.2019.01.001

Figure Lengend Snippet: (A) In the absence of midostaurin, anticancer drugs (grey circles) are effluxed out of ABCB1-overepressing cancer cells by ABCB1 (green), preventing the accumulation of therapeutic drugs in cancer cells, which leads to the MDR phenotype. (B) In the presence of midostaurin, the drug effux function of ABCB1 is blocked by midostaurin and the chemosensitivity of ABCB1-overexpressing cancer cells is hence restored. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Article Snippet: Collectively, our results indicate that midostaurin interacts at the drug-binding pocket of ABCB1 and inhibits the activity of ABCB1. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Fig. 6. caption a7 caption a8 Docking of midostaurin in the drug-binding pocket of ABCB1. (A) The homology model of ABCB1, based on the PDB:5KPI mouse P-glycoprotein structure, was used for exhaustive docking using AutoDock Vina software.

Techniques: