ArticlePeerJ2013
ABT-737, a small molecule Bcl-2/Bcl-xL antagonist, increases antimitotic-mediated apoptosis in human prostate cancer cells.
Article in PeerJ, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- From Platelet Toxicity to Precision Targeting: Evolving Strategies to Overcome Thrombocytopenia in BCL-2/BCL-XL Inhibition.Health science reports · 2026Article
- ABT-737 efficiently inhibits hepatocellular carcinoma cell activity via regulating PANoptosis.Discover oncology · 2026Article
- Unveiling the potential targets and mechanisms of DEHP/BPA exposure on PCOS: insights from network toxicology and molecular docking.Journal of ovarian research · 2025Article
- Review
- Extracellular Matrix Stiffness Enhancement Promotes Docetaxel Resistance in Prostate Cancer via Inhibition of Apoptosis Mediated by Upregulation of PRRX1.International journal of medical sciences · 2025Article
- Article
- Novel BH4-BCL-2 Domain Antagonists Induce BCL-2-Mediated Apoptosis in Triple-Negative Breast Cancer.Cancers · 2022Article
- Mechanisms of cancer cell death induction by paclitaxel: an updated review.Apoptosis : an international journal on programmed cell death · 2022Review
- Repurposing BCL-2 and Jak 1/2 inhibitors: Cure and treatment of HIV-1 and other viral infections.Frontiers in immunology · 2022Review
- Targeting the Intrinsic Apoptosis Pathway: A Window of Opportunity for Prostate Cancer.Cancers · 2021Review
- Dual Akt and Bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell lines.Molecular biology reports · 2021Article
- Novel Therapies in Myeloproliferative Neoplasms: Beyond JAK Inhibitor Monotherapy.Journal of immunotherapy and precision oncology · 2021Review
- Mechanisms of Taxane ResistanceCancers · 2020Review
- Gut Microbiome Critically Impacts PCB-induced Changes in Metabolic Fingerprints and the Hepatic Transcriptome in Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- AT101 [(-)-Gossypol] Selectively Inhibits MCL1 and Sensitizes Carcinoma to BH3 Mimetics by Inducing and Stabilizing NOXA.Cancers · 2020Article
- Activation of Piezo1 sensitizes cells to TRAIL-mediated apoptosis through mitochondrial outer membrane permeability.Cell death & disease · 2019Article
- Review
- Inhibiting Multiple Deubiquitinases to Reduce Androgen Receptor Expression in Prostate Cancer Cells.Scientific reports · 2018Article
- Bcl-2 inhibition sensitizes triple-negative human breast cancer cells to doxorubicin.Oncotarget · 2018Article
- Synergistic cytotoxicity of a prostate cancer-specific immunotoxin in combination with the BH3 mimetic ABT-737.Cancer immunology, immunotherapy : CII · 2018Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Castration-resistant prostate cancer (CRPC) expresses high levels of the anti-apoptotic proteins Bcl-2, Bcl-xL and Mcl-1, resulting in resistance to apoptosis and association with poor prognosis. Docetaxel, an antimitotic drug that is the first-line treatment strategy for CRPC, is known to provide a small survival benefit. However, docetaxel chemotherapy alone is not enough to counteract the high levels of Bcl-2/Bcl-xL/Mcl-1 present in CRPC. ABT-737 is a small molecule that binds to Bcl-2/Bcl-xL (but not Mcl-1) with high affinity and disrupts their interaction with pro-apoptotic Bax/Bak, thus enhancing apoptosis. Our results indicate that ABT-737 can sensitize androgen-dependent LNCaP and CRPC PC3 cells to docetaxel- and to the novel antimitotic ENMD-1198-mediated caspase-dependent apoptosis. CRPC DU145 cells, however, are more resistant to ABT-737 because they are Bax null and not because they express the highest levels of anti-apoptotic Mcl-1 (associated with ABT-737 resistance). Knockdown of Bax or Bak in LNCaP indicates that ABT-737-induced antimitotic enhancement of apoptosis is more dependent on the levels of Bax than Bak. Furthermore, we find that the ability of docetaxel to increase cyclin B1/Cdk1-mediated phosphorylation of Bcl-2/Bcl-xL and decrease Mcl-1 is required for ABT-737 to enhance apoptosis in PC3 cells, as determined by addition of Cdk1 inhibitor purvalanol A and expression of shRNA specific for cyclin B1. Overall, our data suggests that the high levels of anti-apoptotic proteins in Bax-expressing CRPC cells can be overcome by targeting Bcl-2/Bcl-xL with ABT-737 and Mcl-1 with antimitotics.
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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.