Membrane effects of the antitumor drugs doxorubicin and thaliblastine: comparison to multidrug resistance modulators verapamil and trans-flupentixol.
The interactions of the antitumor drugs doxorubicin and thaliblastine with model membranes composed of neutral (phosphatidylcholine) and negatively charged (phosphatidylserine) phospholipids were studied by differential scanning calorimetry and nuclear magnetic resonance. The membrane activities of doxorubicin and thaliblastine were compared to those of the powerful multidrug resistance (MDR) modulators trans-flupentixol and verapamil. The results point out to the potential role of the drug-membrane interactions for the effects of doxorubicin and thaliblastine in resistant tumor cells. They direct also to the artificial membranes as a suitable tool for screening of compounds with potential ability to modulate MDR.
Pajeva
Ilza
I
Centre of Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 105, 1113, Sofia, Bulgaria. pajeva@bio.bas.bg
Todorov
Dimiter K
DK
Seydel
Joachim
J
D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D001060:Aporphines / Q000737:chemistry*; D044182:Benzylisoquinolines / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D004317:Doxorubicin / Q000737:chemistry*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005475:Flupenthixol / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008954:Models, Biological; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D014700:Verapamil / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D001060:Aporphines; D044182:Benzylisoquinolines; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D004317:Doxorubicin; C073328:thalicarpine; D014700:Verapamil; D005475:Flupenthixol