ArticleJournal of cancer research and clinical oncology2008
Bendamustine induces G2 cell cycle arrest and apoptosis in myeloma cells: the role of ATM-Chk2-Cdc25A and ATM-p53-p21-pathways.
Article in Journal of cancer research and clinical oncology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02424851 (A Study of Thalidomide, Bendamustine and Dexamethasone), which is not on this map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Study of Thalidomide, Bendamustine and Dexamethasone (BTD) Versus Bortezomib, Bendamustine and Dexamethasone (BBD) in Patients With Renal Failure Defined as a GFR Below 30 Mls/Min
Who cites it
35 citing papers in PubMed, 70 citations in OpenAlex.
- Investigation of bendamustine HCL in a phase 2 study in women with resistant ovarian cancer.Investigational new drugs · 2013Trial
- Trial
- Microbiota-derived urolithin A in monoclonal gammopathies and multiple myeloma therapy.Microbiome · 2025Article
- The Interplay between the DNA Damage Response (DDR) Network and the Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway in Multiple Myeloma.International journal of molecular sciences · 2024Review
- STAT3 and PD-L1 are negatively correlated with ATM and have impact on the prognosis of triple-negative breast cancer patients with low ATM expression.Breast cancer research and treatment · 2022Article
- Bendamustine: A review of pharmacology, clinical use and immunological effects (Review).Oncology reports · 2022Review
- ALDOA inhibits cell cycle arrest induced by DNA damage via the ATM-PLK1 pathway in pancreatic cancer cells.Cancer cell international · 2021Article
- Review
- RAD52 aptamer regulates DNA damage repair and STAT3 in BRCA1/BRCA2‑deficient human acute myeloid leukemia.Oncology reports · 2020Article
- Bendamustine Conditioning Skews Murine Host DCs Toward Pre-cDC1s and Reduces GvHD Independently of Batf3.Frontiers in immunology · 2020Article
- PKCδ promotes fertilization of mouse embryos in early development via the Cdc25B signaling pathway.Experimental and therapeutic medicine · 2019Article
- Downregulation of long non-coding RNA GAS5 promotes cell proliferation, migration and invasion in esophageal squamous cell carcinoma.Oncology letters · 2018Article
- Tip60 is associated with resistance to X-ray irradiation in prostate cancer.FEBS open bio · 2018Article
- Simultaneous targeting of ATM and Mcl-1 increases cisplatin sensitivity of cisplatin-resistant non-small cell lung cancer.Cancer biology & therapy · 2017Article
- A Systematic Review of the Immune-Regulating and Anticancer Activities of Pseudolaric Acid B.Frontiers in pharmacology · 2017Review
- Review
- Article
- Esters of Bendamustine Are by Far More Potent Cytotoxic Agents than the Parent Compound against Human Sarcoma and Carcinoma Cells.PloS one · 2015Article
- Evaluation of bendamustine in combination with fludarabine in primary chronic lymphocytic leukemia cells.Blood · 2014Article
- Severe Liver Damage and Nonallergic Bronchitis with Eosinophilia in a Patient with Follicular Lymphoma Treated with Bendamustine plus Rituximab.Case reports in oncology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMultiple myeloma is a fatal hematological disease caused by malignant transformation of plasma cells. Bendamustine has been proven to be a potent alternative to melphalan in phase 3 studies, yet its molecular mode of action is still poorly understood.
methodsThe four-myeloma cell lines NCI-H929, OPM-2, RPMI-8226, and U266 were cultured in vitro. Apoptosis was measured by flow cytometry after annexin V FITC and propidium iodide staining. Cell cycle distribution of cells was determined by DNA staining with propidium iodide. Intracellular levels of (phosphorylated) proteins were determined by western blot.
resultsWe show that bendamustine induces apoptosis with an IC50 of 35-65 mug/ml and with cleavage of caspase 3. Incubation with 10-30 mug/ml results in G2 cell cycle arrest in all four-cell lines. The primary DNA-damage signaling kinases ATM and Chk2, but not ATR and Chk1, are activated. The Chk2 substrate Cdc25A phosphatase is degraded and Cdc2 is inhibited by inhibitory phosphorylation of Tyr15 accompanied by increased cyclin B levels. Additionally, p53 activation occurs as phosphorylation of Ser15, the phosphorylation site for ATM. p53 promotes Cdc2 inhibition by upregulation of p21. Targeting of p38 MAPK by the selective inhibitor SB202190 significantly increases bendamustine induced apoptosis. Additionally, SB202190 completely abrogates G2 cell cycle arrest.
conclusionBendamustine induces ATM-Chk2-Cdc2-mediated G2 arrest and p53 mediated apoptosis. Inhibition of p38 MAPK augments apoptosis and abrogates G2 arrest and can be considered as a new therapeutic strategy in combination with bendamustine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.