Cytosine arabinoside potentiates the apoptotic effect of bendamustine on several B- and T-cell leukemia/lymphoma cells and cell lines

Abstract

Bendamustine and cytosine arabinoside (ara-c) are commonly used cytotoxic agents with unique mechanisms of action. We have previously reported a striking additive cytotoxic effect of the consecutive combination of bendamustine and ara-c in mantle cell lymphoma (MCL) cell lines. In the present study, cell lines of follicular lymphoma (DOHH-2), chronic lymphocytic leukemia/lymphoma (EHEB), diffuse large B-cell lymphoma (SU-DHL-4), T-cell leukemia/lymphoma (JURKAT and KARPAS-299) and MCL (JEKO-1 and GRANTA-519) were exposed to the two single drugs or the drugs combined, given simultaneously and consecutively. Peripheral blood chronic lymphocytic leukemia (CLL) B-cells from five patients were also analyzed. Apoptosis, cell proliferation/metabolic activity and mitochondrial damage were evaluated. The combination index (CI) was used to assess synergy between the drugs. Bendamustine exhibited a relevant cytotoxic effect that was dose- and time-dependent, except for SU-DHL-4 and T-cell lymphoma cells. The addition of ara-c after bendamustine significantly potentiated the single-drug cytotoxic effect of bendamustine on all cell lines, including 17p − CLL B-cells, JURKAT and SU-DHL-4, the latter presenting the highest synergism (CI < 0.01). Bendamustine and ara-c are highly synergistic on T- and B-cell lymphoma cells and cell lines, similar to MCL, overcoming resistance to the single agents.

Keywords::

• Bendamustine
• cytarabine
• B-cell lymphoma
• T-cell lymphoma
• 17p − CLL
• R-BAC

Acknowledgements

This work was supported in part by grants from AViLL/AIL (Associazione Vicentina per le Leucemie, i Linfomi e il Mieloma/Associazione Italiana Leucemie), Vicenza, Italy and from Fondazione Progetto Ematologia (Hematology Project Foundation), Vicenza, Italy. Fondazione Progetto Ematologia received a grant from Mundipharma International Ltd to partially cover the cost of the materials used in this study.

The authors would like to thank Dr. Giuseppe Astori for his useful and appreciated comments.

Potential conflict of interest

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