Abstract. We examined in vitro sensitivity of B-CLL cells exposed to cladribine, mafosfamide, mitoxantrone and combinations of cladribine with mafosfamide and/or mitoxantrone. The results revealed that each applied treatment of leukemic cells, besides having a cytotoxic effect, affected the events associated with apoptosis. All drugs used alone, and cladribine combinations with mafosfamide and/or mitoxantrone induced DNA fragmentation and the changes in expression/proteolysis level of caspase-3, caspase-9 precursors, PARP-1, lamin B, Bax and Bcl-2; however, each to a different degree. The exposure of leukemic cells to both cladribine combinations induced stronger effects. Moreover, the data showed that the expression of regulatory antiapoptotic protein Bcl-2 generally decreased in drug-treated B-CLL cells, whereas proapoptotic polypeptide Bax increased, resulting in enhancement of Bax-Bcl-2 ratios in comparison with untreated cells. Drug-treatment of the studied cells induced the translocation of Bax protein from the cytosol to the cellular pellet, containing mitochondria, where this polypeptide indicated the capacity for oligomerization. These observations suggest that the examined drugs are able to induce apoptosis of B-CLL cells via the mitochondria pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.