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

Abstract

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.

Open-label Bendamustine Monotherapy for Pediatric Patients With Relapsed or Refractory Acute Leukemia

“…In vitro analysis of bendamustine in the AML cell line HL-60 indicated modest cytotoxicity6; however, hematologic response was not achieved in a pilot study of bendamustine in adult patients (median age, 69 y) with high-risk AML 11. Although this is a different AML population, these results are consistent with the lack of bendamustine activity observed in childhood AML patients in the present study.…”

“…Bendamustine has also demonstrated cytotoxic activity in the acute myeloid leukemia (AML) cell line HL-60, albeit to a lesser extent than cell lines of lymphoid origin 6. These results suggest that bendamustine may provide a benefit in acute childhood leukemia that warrants studying in the pediatric population.…”

Dose Dependent Effects on Cell Cycle Checkpoints and DNA Repair by Bendamustine

“…We found that only a ∼four-fold difference (50 and 200 µM for adherent cells, 10 and 50 µM for lymphoblast) in concentration can change the cell cycle response from a G2 to an S phase arrest. The maximum concentration of BDM used in this study, 200 µM, to elicit cell cycle perturbations in ‘solid’ cancer cell lines are consistent with the IC50 values obtained in previous studies [12]. While 200 µM is ∼8–13 times higher than clinically achieved [16], [19], the lymphoma cell line U2932 did show the same dose-dependent cell cycle arrest at more clinically relevant concentrations of BDM; cells treated with 10 µM BDM resulted in a G2 arrest, while 25 µM BDM resulted in an S phase arrest.…”

“…1 and Figure S1) in that 50 µM BDM caused a G2 arrest while 200 µM BDM resulted in an S phase arrest. The concentrations of BDM used here are consistent with those previously used against a number of epithelial derived cell lines [11], [12], but are generally higher than concentrations used for leukemic cell lines [12]. To test if this was a feature of adherent cell lines, we treated the U2932 cells (B cell lymphoma) with BDM.…”

Development and validation of sensitive liquid chromatography/tandem mass spectrometry method for quantification of bendamustine in mouse brain tissue

“…Its anticancer mechanisms include inducing the formation of intra-strand and inter-strand crosslinks between DNA bases, causing significant DNA single/double strand breaks, leading to concentration-dependent apoptosis and nonapoptotic cell death or mitotic catastrophe. Both preclinical and clinical studies indicate BM showed better anticancer activities compared with other alkylating agents, likely due to more durable DNA double-strand breaks induced by BM [9,10,11,12]. These properties indicate BM may be useful as a radiosensitizer.…”