Low-Dose Rifabutin Increases Cytotoxicity in Antimitotic-Drug-Treated Resistant Cancer Cells by Exhibiting Strong P-gp-Inhibitory Activity
Abstract
:1. Introduction
2. Results
2.1. VIC + Rifabutin Exhibits Increased Cytotoxicity in P-gp-Overexpressing Drug-Resistant KBV20C Cancer Cells
2.2. Low-Dose Rifabutin Has Strong P-gp-Inhibitory Activity after 4 h of Treatment
2.3. Rifabutin Causes Dose-Dependent Increases in Cytotoxicity in VIC-Treated KBV20C Cells by Inducing Early Apoptosis
2.4. Rifabutin Induces G2-Arrest and Increases DNA Damage in VIC-Treated Resistant KBV20C Cells
2.5. Co-Treatment with Rifabutin Increases the Cytotoxicity of Other Antimitotic Drugs in KBV20C Cells
2.6. Other Antibiotic Drugs (Rifampin, Rifapentine, and Rifaximin) Exhibit Minor P-gp-Inhibitory Activity
3. Discussion
4. Methods and Materials
4.1. Reagents and Cell Culture
4.2. Microscopic Observation
4.3. Cell Viability Assay
4.4. Colony Forming Assay
4.5. Fluorescence-Activated Cell Sorting (FACS) Analysis
4.6. Annexin V Analysis
4.7. Rhodamine123 Uptake Tests
4.8. Western Blot Analysis
4.9. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
Abbreviations
MDR | Multidrug resistance |
P-gp | P-glycoprotein |
FACS | Fluorescence-activated cell sorting |
FDA | United States Food and Drug Administration |
DMSO | Dimethyl sulfoxide |
C-PARP | Cleaved poly ADP ribose polymerase |
ANOVA | One-way analysis of variance |
SDS | Sodium dodecyl sulfate |
PAGE | Polyacrylamide gel electrophoresis |
FITC | Fluorescein isothiocyanate |
PBS | Phosphate-buffered saline |
PI | Propidium iodide |
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Lee, J.S.; Oh, Y.; Kim, H.S.; Yoon, S. Low-Dose Rifabutin Increases Cytotoxicity in Antimitotic-Drug-Treated Resistant Cancer Cells by Exhibiting Strong P-gp-Inhibitory Activity. Int. J. Mol. Sci. 2022, 23, 7383. https://doi.org/10.3390/ijms23137383
Lee JS, Oh Y, Kim HS, Yoon S. Low-Dose Rifabutin Increases Cytotoxicity in Antimitotic-Drug-Treated Resistant Cancer Cells by Exhibiting Strong P-gp-Inhibitory Activity. International Journal of Molecular Sciences. 2022; 23(13):7383. https://doi.org/10.3390/ijms23137383
Chicago/Turabian StyleLee, Ji Sun, Yunmoon Oh, Hyung Sik Kim, and Sungpil Yoon. 2022. "Low-Dose Rifabutin Increases Cytotoxicity in Antimitotic-Drug-Treated Resistant Cancer Cells by Exhibiting Strong P-gp-Inhibitory Activity" International Journal of Molecular Sciences 23, no. 13: 7383. https://doi.org/10.3390/ijms23137383