Induction of "in vitro" apoptosis by fludarabine in freshly isolated B-chronic lymphocytic leukemia cells.
The cytotoxic effects and apoptosis (programmed cell death) induced by fludarabine (FLU), interleukin-2 (IL-2), interleukin-4 (IL-4), IL-2 plus IL-4, alpha-interferon (alpha-IFN), and mafosfamide were evaluated "in vitro" on freshly isolated B-cell chronic lymphocytic leukemia (B-CLL) cells. Cytotoxicity was evaluated according to the soluble tetrazolium/formazan assay. Treatment with mafosfamide, fludarabine, and IL-4 resulted in significant anti-tumor activity against all the freshly isolated samples. On the other hand, no significant cytotoxic activity was observed with alpha-IFN, IL-2, and the combination of IL-2 and IL-4. Apoptosis was evaluated by electrophoresis gel of DNA oligonucleosomal fragments and only FLU significantly activated apoptosis in all the samples. It appears that fludarabine is active against B-CLL cells acting by an direct cytotoxic effect and/or the induction of cell death by apoptosis.
Institute of Haematology, L. e A. Seràgnoli, University of Bologna, Italy.
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PL
Zinzani
M
M
Buzzi
P
P
Farabegoli
P
P
Tosi
A
A
Fortuna
G
G
Visani
G
G
Martinelli
A
A
Zaccaria
S
S
Tura
D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000633:toxicity; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000633:toxicity
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D007376:Interleukin-2; D015847:Interleukin-4; C048341:mafosfamide; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine