Cytotoxic efficacy of bendamustine in human leukemia and breast cancer cell lines

J Cancer Res Clin Oncol. 2002 May;128(5):271-8. doi: 10.1007/s00432-002-0331-8.


Purpose: The purpose of this study was to characterise bendamustine's cytotoxic and apoptotic activity in a panel of leukemia and breast cancer cell lines in comparison to its clastogenicity in murine bone marrow.

Methods: The cytotoxic effect of bendamustine was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-dye reduction assay. Induction of apoptosis was evidenced by DNA gel electrophoresis, nuclear staining, Western blot poly-(adenosine diphosphate-ribose) polymerase (PARP) cleavage, and flow cytometry. As a measure of hematological toxicity, the formation of chromosomal aberrations was investigated in bone marrow cells isolated from mice treated with low non-toxic doses of bendamustine and lomustine.

Results: Bendamustine was preferably active against leukemic cells of lymphoid origin and was found to induce apoptosis in SKW-3 and BV-173 cells as shown by oligonucleosomal DNA and nuclear fragmentation, PARP cleavage, and formation of a sub-G1 fraction. Myeloid and breast carcinoma cell lines were resistant towards bendamustine with the exception of HL-60 cells which exhibit an intermediate sensitivity. Bendamustine was found to have a very low clastogenic effect as compared with equimolar doses of lomustine.

Conclusion: Taken together, the mode of action of bendamustine includes induction of apoptosis. The specific spectrum of activity and the unexpectedly low clastogenicity support the hypothesis that bendamustine in not a typical alkylating agent but exerts an additional mode of action, possibly as a purine antimetabolite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Bendamustine Hydrochloride
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / pathology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Flow Cytometry
  • HL-60 Cells
  • Humans
  • Leukemia / drug therapy*
  • Leukemia / pathology
  • Mice
  • Nitrogen Mustard Compounds / pharmacology*
  • Nitrogen Mustard Compounds / therapeutic use
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Nitrogen Mustard Compounds
  • Bendamustine Hydrochloride