ArticlePloS one2014
Purine analog-like properties of bendamustine underlie rapid activation of DNA damage response and synergistic effects with pyrimidine analogues in lymphoid malignancies.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- The Direction of Modern Therapies in Waldenström Macroglobulinaemia.Journal of cellular and molecular medicine · 2025Review
- Clinical and molecular landscape of prolonged SARS-CoV-2 infection with resistance to remdesivir in immunocompromised patients.PNAS nexus · 2025Article
- The potential of the South African plant Tulbaghia Violacea Harv for the treatment of triple negative breast cancer.Scientific reports · 2025Article
- Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells.PloS one · 2024Article
- Possible New Histological Prognostic Index for Large B-Cell Lymphoma.Journal of clinical medicine · 2023Article
- Studying the Interaction between Bendamustine and DNA Molecule with SERS Based on AuNPs/ZnClInternational journal of molecular sciences · 2023Article
- Serum IgG and lymphocyte counts are useful for the early detection of infection in patients receiving bendamustine-rituximab therapy.Journal of clinical and experimental hematopathology : JCEH · 2022Article
- Bendamustine: A review of pharmacology, clinical use and immunological effects (Review).Oncology reports · 2022Review
- Review
- Current and Novel Alkylators in Multiple Myeloma.Cancers · 2021Review
- A bendamustine resistance gene signature in diffuse large B-cell lymphoma and multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Autophagy Inhibition Potentiates the Anticancer Effects of a Bendamustine Derivative NL-101 in Acute T Lymphocytic Leukemia.BioMed research international · 2020Article
- Article
- Article
- Japanese apricot extract (MK615) potentiates bendamustine-induced apoptosis via impairment of the DNA damage response in lymphoma cells.Oncology letters · 2017Article
- Lysosomal putative RNA transporter SIDT2 mediates direct uptake of RNA by lysosomes.Autophagy · 2016Article
- Esters of Bendamustine Are by Far More Potent Cytotoxic Agents than the Parent Compound against Human Sarcoma and Carcinoma Cells.PloS one · 2015Article
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Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bendamustine has shown considerable clinical activity against indolent lymphoid malignancies as a single agent or in combination with rituximab, but combination with additional anti-cancer drugs may be required for refractory and/or relapsed cases as well as other intractable tumors. In this study, we attempted to determine suitable anti-cancer drugs to be combined with bendamustine for the treatment of mantle cell lymphoma, diffuse large B-cell lymphoma, aggressive lymphomas and multiple myeloma, all of which are relatively resistant to this drug, and investigated the mechanisms underlying synergism. Isobologram analysis revealed that bendamustine had synergistic effects with alkylating agents (4-hydroperoxy-cyclophosphamide, chlorambucil and melphalan) and pyrimidine analogues (cytosine arabinoside, gemcitabine and decitabine) in HBL-2, B104, Namalwa and U266 cell lines, which represent the above entities respectively. In cell cycle analysis, bendamustine induced late S-phase arrest, which was enhanced by 4-hydroperoxy-cyclophosphamide, and potentiated early S-phase arrest by cytosine arabinoside (Ara-C), followed by a robust increase in the size of sub-G1 fractions. Bendamustine was able to elicit DNA damage response and subsequent apoptosis faster and with shorter exposure than other alkylating agents due to rapid intracellular incorporation via equilibrative nucleoside transporters (ENTs). Furthermore, bendamustine increased the expression of ENT1 at both mRNA and protein levels and enhanced the uptake of Ara-C and subsequent increase in Ara-C triphosphate (Ara-CTP) in HBL-2 cells to an extent comparable with the purine analog fludarabine. These purine analog-like properties of bendamustine may underlie favorable combinations with other alkylators and pyrimidine analogues. Our findings may provide a theoretical basis for the development of more effective bendamustine-based combination therapies.
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