Loxoribine affects fludarabine activity on freshly isolated B-chronic lymphocytic leukemia cells.
Purine analogues like fludarabine have been shown to be superior to conventional therapy for B-cell chronic lymphocytic leukemia (B-CLL). In order to improve the activity of fludarabine, we tested its combination with loxoribine, a guanine ribonucleotide derivative, known to enhance the sensitivity of B-CLL cells to cytotoxic drugs. B-CLL cells from 6 patients were studied; co-incubation with loxoribine 100 microM increased the activity of fludarabine by 12% to 48%, as demonstrated by XTT colorimetric assay; while 1000 microM loxoribine exerted a protective effect. Accordingly, fludarabine-induced apoptosis was enhanced by the addition of loxoribine 1000 microM (39% increase). These results indicate that the combination of loxoribine and fludarabine could be of interest in B-CLL.
Tosi
P
P
Institute of Hematology and Medical Oncology Seràgnoli University of Bologna, Policlinico S. Orsola, Italy.
Zinzani
P L
PL
Pellacani
A
A
Ottaviani
E
E
Magagnoli
M
M
Tura
S
S
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006151:Guanosine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D006151:Guanosine; C068562:loxoribine; D014740:Vidarabine; C024352:fludarabine