Medroxyprogesterone acetate increases anthracyclines uptake in chronic lymphatic leukemia cells: role of nitric oxide and lipid peroxidation.
Anthracyclines are one of the most used drugs in the therapy of several malignant tumors. Unfortunately, its use is still limited by their cardio-toxicity and by the presence of cancer cells resistant to these drugs. In the present study we evaluated the ability of a chemo-sensitizer agent, MPA (Medroxyprogesterone Acetate), to modify anthracyclines intranuclear uptake in normal leukocytes (NL) and in chronic lymphatic leukemia leukocytes (CLL). Moreover we evaluated the role of lipid peroxidation and nitric oxide (NO) production on antracyclines activity and on their combination with MPA. Our data show that MPA significantly increases anthracyclines uptake only in CLL cells and decreases anthracyclines induced lipid peroxidation.
Pagnini
U
U
Department of Structures, Functions and Biological Technologies, University of Naples II, Italy.
Pacilio
C
C
Florio
S
S
Crispino
A
A
Claudio
P P
PP
Giordano
A
A
Pagnini
G
G
D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015255:Idarubicin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000473:pathology*; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008315:Malondialdehyde / Q000032:analysis; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D008563:Membrane Lipids / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D009599:Nitroprusside / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D004791:Enzyme Inhibitors; D008563:Membrane Lipids; D009363:Neoplasm Proteins; D014810:Vitamin E; D009599:Nitroprusside; D009569:Nitric Oxide; D008315:Malondialdehyde; D004317:Doxorubicin; D017258:Medroxyprogesterone Acetate; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D015255:Idarubicin