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

被引：0

作者：

S. Konstantinov

A. Kostovski

M. Topashka-Ancheva

M. Genova

M. Berger

机构：

[1] Lab. for Experimental Chemotherapy,

[2] Dept. of Pharmacology and Toxicology,undefined

[3] Faculty of Pharmacy at the Medical University of Sofia,undefined

[4] 2 Dunav St.,undefined

[5] 1000 Sofia,undefined

[6] Bulgaria,undefined

[7] Inst. of Zoology,undefined

[8] Bulgarian Academy of Sciences,undefined

[9] 1 Tsar Osvoboditel Blvd.,undefined

[10] 1000 Sofia,undefined

[11] Bulgaria,undefined

[12] National Centre for Clinical and Transfusion Hematology,undefined

[13] Lab. for Flow Cytometry,undefined

[14] 6 Plovdivsko pole,undefined

[15] 1156 Sofia,undefined

[16] Bulgaria,undefined

[17] Unit of Toxicology and Chemotherapy,undefined

[18] German Cancer Research Center,undefined

[19] Im Neuenheimer Feld 280,undefined

[20] 69120 Heidelberg,undefined

[21] Germany,undefined

来源：

Journal of Cancer Research and Clinical Oncology | 2002年 / 128卷

关键词：

Bendamustine Lymphoid cells In vitro cytotoxicity Apoptosis Clastogenic effect;

D O I：

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学科分类号：

摘要：

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.

引用

页码：271 / 278

页数：7