a24  (TargetMol)

Journal: Drug Design, Development and Therapy

Article Title: Alisol Triterpenoids Exhibit Triple Modulatory Mechanisms on the Cell Membrane to Overcome Cancer Multidrug Resistance

doi: 10.2147/DDDT.S521116

Figure Lengend Snippet: The cytotoxic IC 50 of treatments on paired cancer cell lines (drug-sensitive and drug-resistant). ( A ) Paclitaxel with or without B23 or A24 on HeLaS3 and KB/VIN. ( B ) Vincristine with or without B23 or A24 on HeLaS3 and KB/VIN. ( C ) Paclitaxel with or without B23 or A24 on MCF-7 and MCF-7/DOX. ( D ) Vincristine with or without B23 or A24 on MCF-7 and MCF-7/DOX. Experiments were performed on different days and repeated at least nine times. Data were presented as mean plus S.E. * indicated p-value < 0.05 compared to the chemotherapeutic drug-only in each group.

Article Snippet: B23 and A24 were purchased from TargetMol Chemicals Inc. (Boston, MA, USA).

Techniques:

Journal: Drug Design, Development and Therapy

Article Title: Alisol Triterpenoids Exhibit Triple Modulatory Mechanisms on the Cell Membrane to Overcome Cancer Multidrug Resistance

doi: 10.2147/DDDT.S521116

Figure Lengend Snippet: The influential events of B23 and A24 on HepG2 and HepG2/VIN cell lines. ( A ) B23 and A24 showed significant elevation in ROS production after 24-h treatment, which was especially obvious in the MDR cell line HepG2/VIN. Menadione (50 μM) was used as a positive control. ( B ) B23 and A24 induced prominent apoptosis after 48-h incubation. Paclitaxel (300 nM for HepG2 and 1500 nM for HepG2/VIN) was used as a positive control. ( C ) B23 and A24 did not show secondary necrosis after 72-h incubation. Paclitaxel (300 nM for HepG2 and 1500 nM for HepG2/VIN) was used as a positive control. Experiments were performed on different days and repeated at least nine times. Data were presented as mean plus S.E. * indicated p-value < 0.05 compared to the control in each group.

Article Snippet: B23 and A24 were purchased from TargetMol Chemicals Inc. (Boston, MA, USA).

Techniques: Positive Control, Incubation, Control

Journal: Drug Design, Development and Therapy

Article Title: Alisol Triterpenoids Exhibit Triple Modulatory Mechanisms on the Cell Membrane to Overcome Cancer Multidrug Resistance

doi: 10.2147/DDDT.S521116

Figure Lengend Snippet: The effects of B23 and A24 on the cell membrane in paired drug-sensitive and drug-resistant cell lines. ( A ) B23 and A24 increased cell membrane fluidity in MDR HepG2/VIN after 72-h treatment. MBCD (2.5 mM) was used as a positive control. ( B ) B23 increased cell membrane fluidity in ABCB1 /Flp-In TM -293, whereas A24 showed effects on both cell lines after 72-h treatment. MBCD (2.5 mM) was used as a positive control. ( C ) B23 and A24 significantly inhibited the efflux function of P-gp and increased calcein retention after 30-min pretreatment in the MDR HepG2/VIN cell line. B23 also showed effects in HepG2. Verapamil (10 μM) was used as a positive control. ( D ) B23 and A24 significantly inhibited the efflux function of P-gp and increased calcein retention after 30-min pretreatment in the drug-resistant ABCB1 /Flp-In TM -293. Verapamil (10 μM) was used as a positive control. Experiments were performed on different days and repeated at least nine times. Data were presented as mean plus S.E. * indicated p-value < 0.05 compared to the control in each group.

Article Snippet: B23 and A24 were purchased from TargetMol Chemicals Inc. (Boston, MA, USA).

Techniques: Membrane, Positive Control, Control

Journal: Drug Design, Development and Therapy

Article Title: Alisol Triterpenoids Exhibit Triple Modulatory Mechanisms on the Cell Membrane to Overcome Cancer Multidrug Resistance

doi: 10.2147/DDDT.S521116

Figure Lengend Snippet: The overall effects of B23 and A24 on the human P-gp. ( A ) B23 (left panel) and A24 (right panel) exhibited a dose-dependent inhibition on the P-gp efflux function (5–20 μM). ( B ) B23 and ( C ) A24 increased the intracellular rhodamine 123 fluorescence dose-dependently (2.5–10 μM). Verapamil (10 μM) was used as a positive control. ( D ) B23 showed a significant down-regulation of ABCB1 gene expression after 72-h treatment, while A24 showed a slight inhibitory effect. ( E ) Representative result and ( F ) quantitative results of P-gp protein expression after 72-h B23 and A24 treatment. ( G ) Results of MDR1 P-gp conformational change. B23 and A24 showed no influence compared to the positive control vinblastine. The fluorescent peaks of B23 and A24 did not move rightward and overlapped with negative control DMSO, while the fluorescent peak of vinblastine moved rightward and exhibited a fluorescence increase. The left panel exhibited representative results, and the right showed quantitative results. Experiments were performed on different days and repeated at least nine times. Data were presented as mean plus S.E. *Indicated p-value < 0.05 compared to the control in each group.

Article Snippet: B23 and A24 were purchased from TargetMol Chemicals Inc. (Boston, MA, USA).

Techniques: Inhibition, Fluorescence, Positive Control, Gene Expression, Expressing, Negative Control, Control

Journal: Drug Design, Development and Therapy

Article Title: Alisol Triterpenoids Exhibit Triple Modulatory Mechanisms on the Cell Membrane to Overcome Cancer Multidrug Resistance

doi: 10.2147/DDDT.S521116

Figure Lengend Snippet: The modulatory mechanisms of B23 and A24 on the TMD of human P-gp. ( A ) B23 exhibited an uncompetitive (upper panel, lines were parallel) and non-competitive (lower panel, lines intersected at X-axis) inhibition on the transport of rhodamine 123 and doxorubicin, respectively. ( B ) A24 exhibited competitive inhibition (lines intersected at Y-axis) on the transport of rhodamine 123 and doxorubicin. Data were presented as mean plus S.E. * indicated p-value < 0.05 compared to the control in each group. Experiments were performed on different days and repeated at least nine times. ( C ) The wholescale results of molecular docking between human P-gp (PDB: 7O9W) and B23 or A24 (labeled green color) at the TMD drug-binding site. ( D ) The top view results of molecular docking between human P-gp (PDB: 7O9W) and five ligands (labeled green color) at the TMD drug-binding site. For comparison, doxorubicin, Hoechst 33342, and verapamil were adopted as the site-binding positive controls.

Article Snippet: B23 and A24 were purchased from TargetMol Chemicals Inc. (Boston, MA, USA).

Techniques: Inhibition, Control, Labeling, Binding Assay, Comparison

Journal: Drug Design, Development and Therapy

Article Title: Alisol Triterpenoids Exhibit Triple Modulatory Mechanisms on the Cell Membrane to Overcome Cancer Multidrug Resistance

doi: 10.2147/DDDT.S521116

Figure Lengend Snippet: The modulatory mechanisms of B23 and A24 on the NBD of human P-gp. ( A ) B23 stimulated the basal P-gp ATPase activity but inhibited the verapamil-stimulated ATPase activity. ( B ) A24 stimulated both the basal P-gp ATPase activity and the verapamil-stimulated ATPase activity. Data were presented as mean plus S.E. * and # indicated p-value < 0.05 compared to the control in each group. Experiments were performed on different days and repeated at least nine times. ( C ) The wholescale results of molecular docking between human P-gp (PDB: 7O9W) and three ligands (labeled pink color) at the NBD ATP-binding site. For comparison, verapamil was adopted as the positive control.

Article Snippet: B23 and A24 were purchased from TargetMol Chemicals Inc. (Boston, MA, USA).

Techniques: Activity Assay, Control, Labeling, Binding Assay, Comparison, Positive Control