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Effect of combination of suboptimal concentrations of P-glycoprotein blockers on the proliferation of MDR1 gene expressing cells.
- Source :
-
International journal of cancer [Int J Cancer] 1996 Jan 26; Vol. 65 (3), pp. 389-97. - Publication Year :
- 1996
-
Abstract
- Pharmacologically active in vivo doses of P-glycoprotein (Pgp) blockers, specifically verapamil, Cremophor EL and PSC833 cause toxicity in addition to that from the concomitantly used cancer chemotherapeutic drugs. It was shown before that these blockers cause different types of toxicities in vivo. We found that these 3 chemically distinct Pgp blockers exert different biophysical effects on the membranes of L1210 MDR cells. They also affect the general metabolism of these cells differently, but all block affinity labeling of Pgp. We could also show that the combination of suboptimal doses of these blockers can restore the uptake of the Pgp substrate rhodamine 123 into L1210MDR, 3T3MDR and KB-VI cells and can reduce the survival rate of these cells when treated in combination with daunorubicin. Our results suggest that the combination of suboptimal doses of these Pgp blockers may be advantageous in clinical practice.
- Subjects :
- Cell Division drug effects
Cell Membrane drug effects
Glycerol pharmacology
Humans
Leukemia
Transfection
Tumor Cells, Cultured
ATP Binding Cassette Transporter, Subfamily B, Member 1 antagonists & inhibitors
ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics
Calcium Channel Blockers pharmacology
Cell Membrane metabolism
Cyclosporins pharmacology
Glycerol analogs & derivatives
Verapamil pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0020-7136
- Volume :
- 65
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 8575863
- Full Text :
- https://doi.org/10.1002/(SICI)1097-0215(19960126)65:3<389::AID-IJC19>3.0.CO;2-5