ArticleCell death & disease2015
Synergistic killing of human small cell lung cancer cells by the Bcl-2-inositol 1,4,5-trisphosphate receptor disruptor BIRD-2 and the BH3-mimetic ABT-263.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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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
26 citing papers in PubMed, 47 citations in OpenAlex.
- Mitochondria-ER crosstalk via MAMS: Bridging cellular homeostasis and cancer progression.Apoptosis : an international journal on programmed cell death · 2026Review
- The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- TMCO1 is upregulated in breast cancer and regulates the response to pro-apoptotic agents in breast cancer cells.Cell death discovery · 2024Article
- Calcium's Role in Orchestrating Cancer Apoptosis: Mitochondrial-Centric Perspective.International journal of molecular sciences · 2023Review
- Mitochondria-associated endoplasmic reticulum membrane: Overview and inextricable link with cancer.Journal of cellular and molecular medicine · 2023Review
- Bcl-2 Family of Proteins in the Control of Mitochondrial Calcium Signalling: An Old Chap with New Roles.International journal of molecular sciences · 2021Review
- Network Analysis Identifies Drug Targets and Small Molecules to Modulate Apoptosis Resistant Cancers.Cancers · 2021Article
- IPProgress in molecular and subcellular biology · 2021Review
- Genomic and pathological heterogeneity in clinically diagnosed small cell lung cancer in never/light smokers identifies therapeutically targetable alterations.Molecular oncology · 2021Article
- BDA-366, a putative Bcl-2 BH4 domain antagonist, induces apoptosis independently of Bcl-2 in a variety of cancer cell models.Cell death & disease · 2020Article
- Lessons from the Endoplasmic Reticulum CaCells · 2020Review
- Bcl-2-Protein Family as Modulators of IPCold Spring Harbor perspectives in biology · 2020Review
- Partners in Crime: Towards New Ways of Targeting Calcium Channels.International journal of molecular sciences · 2019Review
- Bcl-2 and IPCellular and molecular life sciences : CMLS · 2019Article
- Creating a New Cancer Therapeutic Agent by Targeting the Interaction between Bcl-2 and IPCold Spring Harbor perspectives in biology · 2019Review
- Constitutive IPCell death and differentiation · 2019Article
- Targeting Bcl-2-IPBiochimica et biophysica acta. Molecular cell research · 2018Review
- Article
- Emerging molecular mechanisms in chemotherapy: CaCell death & disease · 2018Review
- Extracellular and ER-stored CaCell death discovery · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Small cell lung cancer (SCLC) has an annual mortality approaching that of breast and prostate cancer. Although sensitive to initial chemotherapy, SCLC rapidly develops resistance, leading to less effective second-line therapies. SCLC cells often overexpress Bcl-2, which protects cells from apoptosis both by sequestering pro-apoptotic family members and by modulating inositol 1,4,5-trisphosphate receptor (IP3R)-mediated calcium signaling. BH3-mimetic agents such as ABT-263 disrupt the former activity but have limited activity in SCLC patients. Here we report for the first time that Bcl-2-IP3 receptor disruptor-2 (BIRD-2), a decoy peptide that binds to the BH4 domain of Bcl-2 and prevents Bcl-2 interaction with IP3Rs, induces cell death in a wide range of SCLC lines, including ABT-263-resistant lines. BIRD-2-induced death of SCLC cells appears to be a form of caspase-independent apoptosis mediated by calpain activation. By targeting different regions of the Bcl-2 protein and different mechanisms of action, BIRD-2 and ABT-263 induce cell death synergistically. Based on these findings, we propose that targeting the Bcl-2-IP3R interaction be pursued as a novel therapeutic strategy for SCLC, either by developing BIRD-2 itself as a therapeutic agent or by developing small-molecule inhibitors that mimic BIRD-2.
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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.