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.
Zinzani
P L
PL
Institute of Hematology, L.e A. Seràgnoli, University of Bologna, Italy.
Tosi
P
P
Visani
G
G
Martinelli
G
G
Farabegoli
P
P
Buzzi
M
M
Ottaviani
E
E
Salvucci
M
M
Bendandi
M
M
Zaccaria
A
A
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