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Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B‐chronic lymphocytic leukaemia cells
Author(s) -
Bellosillo Beatriz,
Colomer Dolors,
Pons Gabriel,
Gil Joan
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.00520.x
Subject(s) - mitoxantrone , fludarabine , topoisomerase , apoptosis , chronic lymphocytic leukemia , cytotoxic t cell , pharmacology , chemotherapy , chemistry , medicine , cancer research , biology , immunology , leukemia , in vitro , biochemistry , cyclophosphamide
B‐chronic lymphocytic leukaemia (B‐CLL) is characterized by the accumulation of long‐lived CD5 + B lymphocytes. The effect of mitoxantrone, a topoisomerase II inhibitor, on B‐CLL cells was studied. Treatment of B‐CLL cells for 48 h with mitoxantrone (0.5 μg/ml) induced a decrease in cell viability as determined by MTT assay. The IC 50 calculated for the cells of three patients was 0.7 μg/ml for two of them and 1.4 μg/ml for the third. In all three patients the maximum effect was observed with 2 μg/ml. An additive cytotoxic effect was observed when mitoxantrone (0.5 μg/ml) was combined with fludarabine (5 μg/ml). Mitoxantrone induced DNA fragmentation and the proteolytic cleavage of poly(ADP‐ribose) polymerase (PARP), a marker of the activation of caspases, in all the patients studied, demonstrating that the cytotoxic effect of mitoxantrone was due to induction of apoptosis. These results suggest that mitoxantrone, and possibly other topoisomerase II inhibitors, may be used in the chemotherapy of B‐CLL, and that combination of mitoxantrone with fludarabine or other drugs could improve the effectiveness of the treatment.