ArticleApoptosis : an international journal on programmed cell death2010
Bcl-2 inhibits apoptosis by increasing the time-to-death and intrinsic cell-to-cell variations in the mitochondrial pathway of cell death.
Article in Apoptosis : an international journal on programmed cell death, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 81 citations in OpenAlex.
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- Dynamical analysis of a model of BCL-2-dependent cellular decision making.NPJ systems biology and applications · 2025Article
- Thrombomodulin is essential for recombinant Fc-fusion protein production in Chinese hamster ovary cells via multiple signaling pathways.Journal of biological engineering · 2025Article
- Stereotyped Subclones Revealed by High-Density Single-Cell Lineage Tracing Support Robust Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Histological, immunohistochemical assessment and DNA fingerprint species identification of some meat products in Egypt.Scientific reports · 2025Article
- Effect of Pimecrolimus on apoptotic pathways in HToxicology research · 2025Article
- Long-term Cu exposure alters CYP450s activity and induces jejunum injury and apoptosis in broilers.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Article
- N-Acetylcysteine Alleviates D-Galactose-Induced Injury of Ovarian Granulosa Cells in Female Rabbits by Regulating the PI3K/Akt/mTOR Signaling Pathway.Antioxidants (Basel, Switzerland) · 2024Article
- Combination Treatment with Liposomal Doxorubicin and Inductive Moderate Hyperthermia for Sarcoma Saos-2 Cells.Pharmaceuticals (Basel, Switzerland) · 2024Article
- The Role of Hydrogen Sulfide in the Localization and Expression of p53 and Cell Death in the Nervous Tissue in Traumatic Brain Injury and Axotomy.International journal of molecular sciences · 2023Article
- An integrative systems biology approach to overcome venetoclax resistance in acute myeloid leukemia.PLoS computational biology · 2022Article
- Bisphenols A and F, but not S, induce apoptosis in bovine granulosa cellsFrontiers in endocrinology · 2022Article
- The effect of narcotics on ferroptosis-related molecular mechanisms and signalling pathways.Frontiers in pharmacology · 2022Review
- Cordycepin enhances radiosensitivity to induce apoptosis through cell cycle arrest, caspase pathway and ER stress in MA-10 mouse Leydig tumor cells.American journal of cancer research · 2022Article
- Acute toxicity analysis of an inhibitor of BCL2, Disarib, in rats.Scientific reports · 2021Article
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- Paeonol inhibits proliferation and induces cell apoptosis of human T24 and 5637 bladder cancer cells in vitro and in vivo.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- Single-cell microfluidic impedance cytometry: from raw signals to cell phenotypes using data analytics.Lab on a chip · 2021Article
- Induction of cell death and modulation of Annexin A1 by phytoestrogens in human leukemic cell lines.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BH3 mimetics have been proposed as new anticancer therapeutics. They target anti-apoptotic Bcl-2 proteins, up-regulation of which has been implicated in the resistance of many cancer cells, particularly leukemia and lymphoma cells, to apoptosis. Using probabilistic computational modeling of the mitochondrial pathway of apoptosis, verified by single-cell experimental observations, we develop a model of Bcl-2 inhibition of apoptosis. Our results clarify how Bcl-2 imparts its anti-apoptotic role by increasing the time-to-death and cell-to-cell variability. We also show that although the commitment to death is highly impacted by differences in protein levels at the time of stimulation, inherent stochastic fluctuations in apoptotic signaling are sufficient to induce cell-to-cell variability and to allow single cells to escape death. This study suggests that intrinsic cell-to-cell stochastic variability in apoptotic signaling is sufficient to cause fractional killing of cancer cells after exposure to BH3 mimetics. This is an unanticipated facet of cancer chemoresistance.
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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.