ArticlePloS one2008
M867, a novel selective inhibitor of caspase-3 enhances cell death and extends tumor growth delay in irradiated lung cancer models.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Caspases as master regulators of programmed cell death: apoptosis, pyroptosis and beyond.Experimental & molecular medicine · 2025Review
- Caspases: structural and molecular mechanisms and functions in cell death, innate immunity, and disease.Cell discovery · 2025Review
- The concealed side of caspases: beyond a killer of cells.Cellular and molecular life sciences : CMLS · 2024Review
- Identifying the Multitarget Pharmacological Mechanism of Action of Genistein on Lung Cancer by Integrating Network Pharmacology and Molecular Dynamic Simulation.Molecules (Basel, Switzerland) · 2024Article
- Inhibition of Apoptosis in a Model of Ischemic Stroke Leads to Enhanced Cell Survival, Endogenous Neural Precursor Cell Activation and Improved Functional Outcomes.International journal of molecular sciences · 2024Article
- Research progress on mitochondria regulating tumor immunity.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- A long way to go: caspase inhibitors in clinical use.Cell death & disease · 2021Review
- Review
- Therapy-Induced Tumor Cell Death: Friend or Foe of Immunotherapy?Frontiers in oncology · 2021Review
- Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling.Nature immunology · 2020Article
- Mitochondria as multifaceted regulators of cell death.Nature reviews. Molecular cell biology · 2020Review
- Apoptotic mitochondria prime anti-tumour immunity.Cell death discovery · 2020Article
- Role of autophagy in regulating the radiosensitivity of tumor cells.Journal of cancer research and clinical oncology · 2017Review
- Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency.Nature cell biology · 2017Article
- Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism.Cancer letters · 2017Article
- Autophagy is not uniformly cytoprotective: a personalized medicine approach for autophagy inhibition as a therapeutic strategy in non-small cell lung cancer.Biochimica et biophysica acta · 2016Review
- A fate worse than death: apoptosis as an oncogenic process.Nature reviews. Cancer · 2016Review
- Low levels of Caspase-3 predict favourable response to 5FU-based chemotherapy in advanced colorectal cancer: Caspase-3 inhibition as a therapeutic approach.Cell death & disease · 2016Article
- Article
- Cytoprotective effect of selective small-molecule caspase inhibitors against staurosporine-induced apoptosis.Drug design, development and therapy · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundLung cancer remains the leading cause of cancer death worldwide. Radioresistance of lung cancer cells results in unacceptable rate of loco-regional failure. Although radiation is known to induce apoptosis, our recent study showed that knockdown of pro-apoptotic proteins Bak and Bax resulted in an increase in autophagic cell death and lung cancer radiosensitivity in vitro. To further explore the potential of apoptosis inhibition as a way to sensitize lung cancer for therapy, we tested M867, a novel chemical and reversible caspase-3 inhibitor, in combination with ionizing radiation in vivo and in vitro. METHODS AND
findingsM867 reduced clonogenic survival in H460 lung cancer cells (DER = 1.27, p = 0.007) compared to the vehicle-treated treated cells. We found that administration of M867 with ionizing radiation in an in vivo mouse hind limb lung cancer model was well tolerated, and produced a significant tumor growth delay compared to radiation alone. A dramatic decrease in tumor vasculature was observed with M867 and radiation using von Willebrand factor staining. In addition, Ki67 index showed >5-fold reduction of tumor proliferation in the combination therapy group, despite the reduced levels of apoptosis observed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. Radiosensitizing effect of M867 through inhibiting caspases was validated using caspase-3/-7 double-knockout (DKO) mouse embryonic fibroblasts (MEF) cell model. Consistent with our previous study, autophagy contributed to the mechanism of increased cell death, following inhibition of apoptosis. In addition, matrigel assay showed a decrease in in vitro endothelial tubule formation during the M867/radiation combination treatment.
conclusionsM867 enhances the cytotoxic effects of radiation on lung cancer and its vasculature both in vitro and in vivo. M867 has the potential to prolong tumor growth delay by inhibiting tumor proliferation. Clinical trials are needed to determine the potential of this combination therapy in patients with locally advanced lung cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.