Abstract
Background: Clinical drug resistance is frequently associated with overexpression of the multidrug resistance (MDR) proteins P-glycoprotein (Pgp), multidrug resistance protein (MRP-1) and breast cancer resistance protein (BCRP). Taxanes are substrates for Pgp and MRP-1, but not BCRP. Taxane-based reversal agents (tRAs) are non-cytotoxic MDR modulators previously examined for broad-spectrum modulation of Pgp, MRP-1 and BCRP. Materials and Methods: Modulation by tRAs was studied by flow cytometry and resistance to taxanes was studied in cytotoxicity assays in the parental HL60/wt, 8226/wt and MCF7/S, and the resistant HL60/ADR, 8226/Dox6, 8226/MR20 and MCF7 AdVp3000 cell lines. Amino acid sequence (BLAST) alignments were performed using ClustalW. Results: Structure-activity analysis demonstrated greatest alignment of BCRP with the transmembrane 7-12 region of Pgp and identified tRA side groups that contributed or were detrimental to modulation. Conclusion: Identification of tRA side groups contributing to modulation of Pgp, MRP-1 and BCRP will allow the design of a next generation of tRAs and will optimize their potential clinical applicability.
| Original language | English |
|---|---|
| Pages (from-to) | 409-415 |
| Number of pages | 7 |
| Journal | Anticancer Research |
| Volume | 24 |
| Issue number | 2 A |
| State | Published - Mar 2004 |
Keywords
- Breast cancer resistance protein
- Modulation
- Multidrug resistance
- Multidrug resistance protein
- P-glycoprotein
- Structure-activity analysis
- Taxane
Fingerprint
Dive into the research topics of 'Structure-activity Analysis of Taxane-based Broad-spectrum Multidrug Resistance Modulators'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver