doi: 10.1186/s40880-015-0003-0
ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10 (ABCC10) are not primary resistance factors for cabazitaxel
Rishil J Kathawala, Yi-Jun Wang, Suneet Shukla, Yun-Kai Zhang, Saeed Alqahtani, Amal Kaddoumi, Suresh V Ambudkar, Charles R Ashby and Zhe-Sheng Chen
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens 11439, NY, USA
[Abstract]
Introduction
ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10 (ABCC10) proteins are efflux transporters that couple the energy derived from ATP hydrolysis to the translocation of toxic substances and chemotherapeutic drugs out of cells. Cabazitaxel is a novel taxane that differs from paclitaxel by its lower affinity for ATP-binding cassette (ABC) transporters.
Methods
We determined the effects of cabazitaxel, a novel tubulin-binding taxane, and paclitaxel on paclitaxel-resistant, ABCB1-overexpressing KB-C2 and LLC-MDR1-WT cells and paclitaxel-resistant, ABCC10-overexpressing HEK293/ABCC10 cells by calculating the degree of drug resistance and measuring ATPase activity of the ABCB1 transporter.
Results
Decreased resistance to cabazitaxel compared with paclitaxel was observed in KB-C2, LLC-MDR1-WT, and HEK293/ABCC10 cells. Moreover, cabazitaxel had low efficacy, whereas paclitaxel had high efficacy in stimulating the ATPase activity of ABCB1, indicating a direct interaction of both drugs with the transporter.
Conclusion
ABCB1 and ABCC10 are not primary resistance factors for cabazitaxel compared with paclitaxel, suggesting that cabazitaxel may have a low affinity for these efflux transporters.
Introduction
ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10 (ABCC10) proteins are efflux transporters that couple the energy derived from ATP hydrolysis to the translocation of toxic substances and chemotherapeutic drugs out of cells. Cabazitaxel is a novel taxane that differs from paclitaxel by its lower affinity for ATP-binding cassette (ABC) transporters.
Methods
We determined the effects of cabazitaxel, a novel tubulin-binding taxane, and paclitaxel on paclitaxel-resistant, ABCB1-overexpressing KB-C2 and LLC-MDR1-WT cells and paclitaxel-resistant, ABCC10-overexpressing HEK293/ABCC10 cells by calculating the degree of drug resistance and measuring ATPase activity of the ABCB1 transporter.
Results
Decreased resistance to cabazitaxel compared with paclitaxel was observed in KB-C2, LLC-MDR1-WT, and HEK293/ABCC10 cells. Moreover, cabazitaxel had low efficacy, whereas paclitaxel had high efficacy in stimulating the ATPase activity of ABCB1, indicating a direct interaction of both drugs with the transporter.
Conclusion
ABCB1 and ABCC10 are not primary resistance factors for cabazitaxel compared with paclitaxel, suggesting that cabazitaxel may have a low affinity for these efflux transporters.
Chinese Journal of Cancer 2015, Volume: 34, Issue 3
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Rishil J Kathawala, Yi-Jun Wang, Suneet Shukla, Yun-Kai Zhang, Saeed Alqahtani, Amal Kaddoumi, Suresh V Ambudkar, Charles R Ashby and Zhe-Sheng Chen. ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10 (ABCC10) are not primary resistance factors for cabazitaxel. Chin J Cancer. 2015, 34:5. doi:10.1186/s40880-015-0003-0
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[ Html full-text / Citation export] (BioMed Central)
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Cite this article
Rishil J Kathawala, Yi-Jun Wang, Suneet Shukla, Yun-Kai Zhang, Saeed Alqahtani, Amal Kaddoumi, Suresh V Ambudkar, Charles R Ashby and Zhe-Sheng Chen. ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10 (ABCC10) are not primary resistance factors for cabazitaxel. Chin J Cancer. 2015, 34:5. doi:10.1186/s40880-015-0003-0
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