ArticleCancer research2011
The BH3 mimetic ABT-737 induces cancer cell senescence.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Dual targeting of BCL-XL and MCL-1 exposes a rapid and exploitable apoptotic vulnerability in non-small cell lung cancer.Cell death and differentiation · 2026Article
- Targeting cellular senescence through nutritional senotherapeutics in brain aging and neurodegenerative diseases.Frontiers in nutrition · 2026Review
- Mitochondria and cell death.Nature cell biology · 2024Review
- The caspase-activated DNase promotes cellular senescence.The EMBO journal · 2024Article
- Sublethal engagement of apoptotic pathways in residual cancer.Trends in cell biology · 2024Review
- Article
- Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells.Journal of cellular and molecular medicine · 2023Article
- TLR4 activation induces inflammatory vascular permeability via Dock1 targeting and NOX4 upregulation.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Senescence in Vascular Smooth Muscle Cells and Atherosclerosis.Frontiers in cardiovascular medicine · 2022Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Apoptosis - Fueling the oncogenic fire.The FEBS journal · 2021Review
- Epithelial cell senescence: an adaptive response to pre-carcinogenic stresses?Cellular and molecular life sciences : CMLS · 2017Review
- Executioner caspases and CAD are essential for mutagenesis induced by TRAIL or vincristine.Cell death & disease · 2017Article
- Increased Bcl-xL Expression in Pancreatic Neoplasia Promotes Carcinogenesis by Inhibiting Senescence and Apoptosis.Cellular and molecular gastroenterology and hepatology · 2017Article
- A fate worse than death: apoptosis as an oncogenic process.Nature reviews. Cancer · 2016Review
- Constitutive p53 heightens mitochondrial apoptotic priming and favors cell death induction by BH3 mimetic inhibitors of BCL-xL.Cell death & disease · 2016Article
- Structure-Function Analysis of the Mcl-1 Protein Identifies a Novel Senescence-regulating Domain.The Journal of biological chemistry · 2015Article
- Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer.Cell death and differentiation · 2014Article
- The ratio of Mcl-1 and Noxa determines ABT737 resistance in squamous cell carcinoma of the skin.Cell death & disease · 2014Article
- The putative BH3 mimetic S1 sensitizes leukemia to ABT-737 by increasing reactive oxygen species, inducing endoplasmic reticulum stress, and upregulating the BH3-only protein NOXA.Apoptosis : an international journal on programmed cell death · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
ABT-737, a small molecule cell-permeable Bcl-2 antagonist that acts by mimicking BH3 proteins, induces apoptotic cell death in multiple cancer types. However, when incubated with this agent many solid tumor cell lines do not undergo apoptosis. The current study reveals a novel mechanism whereby ABT-737 when added to apoptosis-resistant cancer cells has profound biologic effects. In PV-10 cells, a renal cell carcinoma that does not die after ABT-737 treatment, this agent induces a two-fold change in the transcription of nearly 430 genes. Many of these induced mRNA changes are in secreted proteins, IL-6, IL-8, and IL-11 and chemokines CXCL2 and CXCL5, or genes associated with an "inflammatory" phenotype. Strikingly, these gene changes are highly similar to those changes previously identified in cellular senescence. Brief exposure of apoptosis-resistant renal, lung and prostate cancer cell lines to ABT-737, although not capable of inducing cell death, causes the induction of senescence-associated β-galactosidase and inhibition of cell growth consistent with the induction of cellular senescence. Evidence indicates that the induction of senescence occurs as a result of reactive oxygen species elevation followed by low-level activation of the caspase cascade, insufficient to induce apoptosis, but sufficient to lead to minor DNA damage and increases in p53, p21, IL-6 and 8 proteins. By overexpression of a dominant-negative p53 protein, we show that ABT-737-induced cellular senescence is p53-dependent. Thus, in multiple cancer types in which ABT-737 is incapable of causing cell death, ABT-737 may have additional cellular activities that make its use as an anticancer agent highly attractive.
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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.