Acquired Drug Resistance Enhances Imidazoquinoline Efflux by P-Glycoprotein
Abstract
:1. Introduction
2. Results
2.1. Imiquimod, Resiquimod, and Gardiquimod Are Substrates of P-gp
2.2. MDR Cancer Cell Lines Enhance P-gp Expression
2.3. Imiquimod Competes with Rhodamine 123 Efflux in MDR-Derived Cancer Cell Lines
2.4. Imiquimod Increases Rhodamine 123 Uptake under Passive Diffusion Conditions
2.5. Resiquimod and Gardiquimod Are Not Passively Taken up by MDR Cancer Cells
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. ATPase Assay
4.3. Western Blot
4.4. Immunofluorescence Assay
4.5. Competitive Efflux Studies with Rhodamine 123
4.6. Uptake Studies with Rhodamine 123
4.7. Cellular Uptake Studies
4.8. Cytotoxicity Assay
5. Conclusions
6. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Imidazoquinoline | cLogP | KD (μM) |
---|---|---|
Imiquimod | 1.428 | 7.66 |
Resiquimod | 0.036 | 24.37 |
Gardiquimod | −0.254 | N.D. |
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Pulukuri, A.J.; Burt, A.J.; Opp, L.K.; McDowell, C.M.; Davaritouchaee, M.; Nielsen, A.E.; Mancini, R.J. Acquired Drug Resistance Enhances Imidazoquinoline Efflux by P-Glycoprotein. Pharmaceuticals 2021, 14, 1292. https://doi.org/10.3390/ph14121292
Pulukuri AJ, Burt AJ, Opp LK, McDowell CM, Davaritouchaee M, Nielsen AE, Mancini RJ. Acquired Drug Resistance Enhances Imidazoquinoline Efflux by P-Glycoprotein. Pharmaceuticals. 2021; 14(12):1292. https://doi.org/10.3390/ph14121292
Chicago/Turabian StylePulukuri, Anunay J., Anthony J. Burt, Larissa K. Opp, Colin M. McDowell, Maryam Davaritouchaee, Amy E. Nielsen, and Rock J. Mancini. 2021. "Acquired Drug Resistance Enhances Imidazoquinoline Efflux by P-Glycoprotein" Pharmaceuticals 14, no. 12: 1292. https://doi.org/10.3390/ph14121292
APA StylePulukuri, A. J., Burt, A. J., Opp, L. K., McDowell, C. M., Davaritouchaee, M., Nielsen, A. E., & Mancini, R. J. (2021). Acquired Drug Resistance Enhances Imidazoquinoline Efflux by P-Glycoprotein. Pharmaceuticals, 14(12), 1292. https://doi.org/10.3390/ph14121292