Modification of membrane fluidity and depolarization by some anthracyclines in different cell lines.
One of the major problems in cancer treatment is the progressive desensitization of cancer cells to chemotherapeutic drugs. Several hypotheses have been advanced to explain this property of cancer cells. In recent years different calcium channel blockers and other chemosensitizing agents like synthetic progestins have been used to revert drug resistance. In our experiments we evaluated the effects of Doxorubicin and Idarubicin on membrane fluidity and depolarization using normal lymphocytes, chronic lymphatic leukemia lymphocytes, normal breast and hormone dependent breast cancer cells and cardiomyocytes. The drugs were used alone or in combination with Verapamil and Medroxyprogesterone acetate. We showed that MPA enhances DOXO and IDA biochemical effects, acting not only on the membrane lipid bilayer, but also on ion channels. VERA instead does not seem to act through the same mechanism.
Pacilio
C
C
Department of Structures, Functions and Biological Technologies, University of Naples Federico II, Italy.
Florio
S
S
Pagnini
U
U
Crispino
A
A
Claudio
P P
PP
Pacilio
G
G
Pagnini
G
G
D000818:Animals; D018943:Anthracyclines / Q000494:pharmacology*; D001943:Breast Neoplasms; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008051:Lipid Bilayers; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008560:Membrane Fluidity / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D018943:Anthracyclines; D008051:Lipid Bilayers; D004317:Doxorubicin; D017258:Medroxyprogesterone Acetate; D014700:Verapamil; D015255:Idarubicin