ArticleMolecular cancer therapeutics2013
Vinblastine rapidly induces NOXA and acutely sensitizes primary chronic lymphocytic leukemia cells to ABT-737.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
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- The first-in-Africa ex vivo drug sensitivity testing platform identifies novel drug combinations for South African leukaemia patient cohort.Scientific reports · 2025Article
- Albendazole inhibits colon cancer progression and therapy resistance by targeting ubiquitin ligase RNF20.British journal of cancer · 2024Article
- A phase I trial of BNC105P and ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia.EJHaem · 2022Article
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Eribulin Activates the cGAS-STING Pathway via the Cytoplasmic Accumulation of Mitochondrial DNA.Molecular pharmacology · 2021Article
- AT101 [(-)-Gossypol] Selectively Inhibits MCL1 and Sensitizes Carcinoma to BH3 Mimetics by Inducing and Stabilizing NOXA.Cancers · 2020Article
- Article
- BH3 mimetic ABT-263 enhances the anticancer effects of apigenin in tumor cells with activating EGFR mutation.Cell & bioscience · 2019Article
- Microtubule destabilising agents: far more than just antimitotic anticancer drugs.British journal of clinical pharmacology · 2017Review
- Improving anticancer drug development begins with cell culture: misinformation perpetrated by the misuse of cytotoxicity assays.Oncotarget · 2017Review
- Cell Cycle-Dependent Mechanisms Underlie Vincristine-Induced Death of Primary Acute Lymphoblastic Leukemia Cells.Cancer research · 2016Article
- Natural compounds for pediatric cancer treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2016Review
- Rapid induction of apoptosis in chronic lymphocytic leukemia cells by the microtubule disrupting agent BNC105.Cancer biology & therapy · 2016Article
- Vincristine activates c-Jun N-terminal kinase in chronic lymphocytic leukaemia in vivo.British journal of clinical pharmacology · 2015Article
- Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells.PloS one · 2015Article
- Apoptosis inducers in chronic lymphocytic leukemia.Oncotarget · 2014Review
- Noxa and cancer therapy: Tuning up the mitochondrial death machinery in response to chemotherapy.Molecular & cellular oncology · 2014Review
- Toward a cure for chronic lymphocytic leukemia: an attack on multiple fronts.Expert review of anticancer therapy · 2013Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Proteins of the BCL2 family provide a survival mechanism in many human malignancies, including chronic lymphocytic leukemia (CLL). The BCL2 inhibitor ABT-263 (navitoclax) is active in clinical trials for lymphoid malignancies, yet resistance is expected on the basis of preclinical models. We recently showed that vinblastine can dramatically sensitize several leukemia cell lines to ABT-737 (the experimental congener of ABT-263). The goal of these experiments was to determine the impact of vinblastine on ABT-737 sensitivity in CLL cells isolated from peripheral blood and to define the underlying mechanism. Freshly isolated CLL cells from 35 patients, as well as normal lymphocytes and platelets, were incubated with various microtubule-disrupting agents plus ABT-737 to assess sensitivity to the single agents and the combination. ABT-737 and vinblastine displayed a range of sensitivity as single agents, and vinblastine markedly sensitized all CLL samples to ABT-737 within six hours. Vinblastine potently induced the proapoptotic protein PMAIP1 (NOXA) in both time- and dose-dependent manner and this was required for the observed apoptosis. Combretastatin A4, which dissociates microtubules by binding to a different site, had the same effect, confirming that interaction of these agents with microtubules is the initial target. Similarly, vincristine and vinorelbine induced NOXA and enhanced CLL sensitivity to ABT-737. Furthermore, vinblastine plus ABT-737 overcame stroma-mediated resistance to ABT-737 alone. Apoptosis was induced with clinically achievable concentrations with no additional toxicity to normal lymphocytes or platelets. These results suggest that vinca alkaloids may improve the clinical efficacy of ABT-263 in patients with CLL.
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