Apoptosis induction with three nucleoside analogs on freshly isolated B-chronic lymphocytic leukemia cells.
The cytotoxic effects and the induction of programmed cell death (apoptosis) by Fludarabine (FLU), 2-chlorodeoxyadenosine (2-CdA), and deoxycoformycin (DCF) with/without alpha-interferon (alpha-IFN) were evaluated in vitro against freshly isolated B-chronic lymphocytic leukemia (B-CLL) cells. Cytotoxicity was evaluated according to the soluble tetrazolium/formazan assay. Regarding the cytotoxicity, FLU, 2-CdA, and DCF showed a mean antitumor activity of 45% +/- 3.39 (mean +/- S.D.), 55% +/- 4.72, and 20% +/- 3.16, respectively. alpha-IFN alone showed a mean cytotoxic activity of 10% +/- 2.72. The cytotoxicity of these purine analogues in combination with alpha-IFN was 52% +/- 2.97, 75% +/- 3.41, and 26% +/- 7.09, respectively. We observed a statistically significant increase of cytotoxicity compared to controls in FLU alone (P < 0.05), 2-CdA (P < 0.05), and their combination with alpha-IFN (P < 0.05). Apoptosis was evaluated by electrophoresis gel of DNA oligonucleosomal fragments and by a cytofluorimetric method. Only FLU and 2-CdA activated the apoptosis and DCF showed a minor apoptotic pathway amount. These apoptosis data were confirmed by both gel electrophoresis of DNA and by propidium iodide cytofluorimetric method. FLU and 2-CdA show activity in B-CLL cells by direct cytotoxic action and the induction of cell death by apoptosis; in the future, it would be interesting to utilize these in vitro assays in monitoring chemosensitivity and predicting response for the clinical use.
Institute of Hematology, L.e A. Seràgnoli, University of Bologna, Italy.
P L
PL
Zinzani
P
P
Tosi
G
G
Visani
G
G
Martinelli
P
P
Farabegoli
M
M
Buzzi
E
E
Ottaviani
M
M
Salvucci
M
M
Bendandi
A
A
Zaccaria
D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D017338:Cladribine / Q000494:pharmacology*; D004249:DNA Damage; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015649:Pentostatin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
D016898:Interferon-alpha; D015649:Pentostatin; D017338:Cladribine; D014740:Vidarabine; C024352:fludarabine