In vitro sensitivity of B-cell chronic lymphocytic leukemia to cladribine and its combinations with mafosfamide and/or mitoxantrone

Agnieszka Kobylinska, Jolanta Bednarek, Jerzy Z. Blonski, Malgorzata Hanausek, Zbigniew Walaszek, Tadeusz Robak, Zofia M. Kilianska

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1389-1395
Number of pages7
JournalOncology reports
Volume16
Issue number6
DOIs
StatePublished - Dec 2006

Keywords

  • Apoptosis-related events
  • B-cell chronic lymphocytic leukemia
  • Chemosensitivity
  • In vitro

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'In vitro sensitivity of B-cell chronic lymphocytic leukemia to cladribine and its combinations with mafosfamide and/or mitoxantrone'. Together they form a unique fingerprint.

Cite this