ArticleScientific reports2015
Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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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
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 174 citations in OpenAlex.
- Ivermectin, a potential anticancer drug derived from an antiparasitic drug.Pharmacological research · 2021Pooled it
- Biomimetic platelet-membrane camouflaged ivermectin nanocrystals for tumor homing and breast cancer management.Drug delivery and translational research · 2026Article
- Calcium and TRPML-Mediated Autophagy: Implications in Cancer, Cardiovascular Diseases, and Cardio-Oncology.Cardiovascular toxicology · 2026Review
- Tumor growth suppression of ivermectin in gastric cancer cell lines and primary gastric cancer organoids.Journal of gastrointestinal oncology · 2026Article
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Abnormal purinergic signaling contributes to development of renal cysts in autosomal dominant polycystic kidney disease.Purinergic signalling · 2026Article
- Natural compounds targeting glycolysis and TME in ovarian cancer: from metabolic crosstalk to therapeutic potential.Frontiers in pharmacology · 2026Review
- P2X7 blockade inhibits the growth of breast cancer in 4T1 breast cancer-bearing mice by NLRP3/caspase 1 pathway.Archives of medical science : AMS · 2026Article
- Breast cancer patients present pro-tumor biomarkers related to purinergic signaling and oxidative stress.Purinergic signalling · 2025Article
- M1-like macrophages regulate T cell infiltration in colorectal cancer through P2X4 receptor.iScience · 2025Article
- Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.Purinergic signalling · 2025Review
- ATP stimulates appetite by enhancing the expression of hypothalamic orexigenic neuropeptides.Molecular brain · 2025Article
- Synergistic Antitumor Effects of Ivermectin and Metformin in Canine Breast Cancer via PI3K/AKT/mTOR Pathway Inhibition.Current issues in molecular biology · 2025Article
- Review
- Cell death in tumor microenvironment: an insight for exploiting novel therapeutic approaches.Cell death discovery · 2025Review
- Ivermectin inhibits epithelial-to-mesenchymal transition via Wnt signaling in endocrine-resistant breast cancer cells.PloS one · 2025Article
- Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway.Acta biochimica et biophysica Sinica · 2024Article
- Novel synthesized ionizable lipid for LNP-mediated P2X7siRNA to inhibit migration and induce apoptosis of breast cancer cells.Purinergic signalling · 2024Article
- Ivermectin Synergizes with Modulated Electro-hyperthermia and Improves Its Anticancer Effects in a Triple-Negative Breast Cancer Mouse Model.ACS pharmacology & translational science · 2024Article
- Synergistically Augmenting Cancer Immunotherapy by Physical Manipulation of Pyroptosis Induction.Phenomics (Cham, Switzerland) · 2024Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Overexpression of P2X7 receptors correlates with tumor growth and metastasis. Yet, release of ATP is associated with immunogenic cancer cell death as well as inflammatory responses caused by necrotic cell death at sites of trauma or ischemia-reperfusion injury. Using an FDA-approved anti-parasitic agent Ivermectin as a prototype agent to allosterically modulate P2X4 receptors, we can switch the balance between the dual pro-survival and cytotoxic functions of purinergic signaling in breast cancer cells. This is mediated through augmented opening of the P2X4/P2X7-gated Pannexin-1 channels that drives a mixed apoptotic and necrotic mode of cell death associated with activation of caspase-1 and is consistent with pyroptosis. We show that cancer cell death is dependent on ATP release and death signals downstream of P2X7 receptors that can be reversed by inhibition of NADPH oxidases-generated ROS, Ca(2+)/Calmodulin-dependent protein kinase II (CaMKII) or mitochondrial permeability transition pore (MPTP). Ivermectin induces autophagy and release of ATP and HMGB1, key mediators of inflammation. Potentiated P2X4/P2X7 signaling can be further linked to the ATP rich tumor microenvironment providing a mechanistic explanation for the tumor selectivity of purinergic receptors modulation and its potential to be used as a platform for integrated cancer immunotherapy.
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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.