ArticlePloS one2012
A novel muscarinic antagonist R2HBJJ inhibits non-small cell lung cancer cell growth and arrests the cell cycle in G0/G1.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- The CAGE Framework (Calcium-Gated Excitability): From Single Neurotransmitters to Calcium States in the Tumor Microenvironment.International journal of molecular sciences · 2026Review
- The role of acetylcholine and its receptors in tumor immune regulation: mechanisms and potential therapeutic targets.Molecular cancer · 2025Review
- Role of the parasympathetic nervous system in cancer initiation and progression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Review
- Potential Role for Combined Subtype-Selective Targeting of MFrontiers in pharmacology · 2021Review
- Review
- Acetylcholine signaling system in progression of lung cancers.Pharmacology & therapeutics · 2019Review
- Exposure to antimuscarinic medications for treatment of overactive bladder and risk of lung cancer and colon cancer.Clinical epidemiology · 2019Article
- Aclidinium inhibits proliferation and metastasis of ovarian cancer SKOV3 cells via downregulating PI3K/AKT/mTOR signaling pathway.Oncology letters · 2018Article
- The insect repellent N,N-diethyl-m-toluamide (DEET) induces angiogenesis via allosteric modulation of the M3 muscarinic receptor in endothelial cells.Scientific reports · 2016Article
- Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia.Frontiers in pharmacology · 2016Article
- Article
- Blocking M2 muscarinic receptor signaling inhibits tumor growth and reverses epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC).Cancer biology & therapy · 2015Article
- High expression of M3 muscarinic acetylcholine receptor is a novel biomarker of poor prognostic in patients with non-small cell lung cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancers express the cholinergic autocrine loop, which facilitates the progression of cancer cells. The antagonists of mAChRs have been demonstrated to depress the growth of small cell lung cancers (SCLCs). In this study we intended to investigate the growth inhibitory effect of R2HBJJ, a novel muscarinic antagonist, on non-small cell lung cancer (NSCLC) cells and the possible mechanisms. The competitive binding assay revealed that R2HBJJ had a high affinity to M3 and M1 AChRs. R2HBJJ presented a strong anticholinergic activity on carbachol-induced contraction of guinea-pig trachea. R2HBJJ markedly suppressed the growth of NSCLC cells, such as H1299, H460 and H157. In H1299 cells, both R2HBJJ and its leading compound R2-PHC displayed significant anti-proliferative activity as M3 receptor antagonist darifenacin. Exogenous replenish of ACh could attenuate R2HBJJ-induced growth inhibition. Silencing M3 receptor or ChAT by specific-siRNAs resulted in a growth inhibition of 55.5% and 37.9% on H1299 cells 96 h post transfection, respectively. Further studies revealed that treatment with R2HBJJ arrested the cell cycle in G0/G1 by down-regulation of cyclin D1-CDK4/6-Rb. Therefore, the current study reveals that NSCLC cells express an autocrine and paracrine cholinergic system which stimulates the growth of NSCLC cells. R2HBJJ, as a novel mAChRs antagonist, can block the local cholinergic loop by antagonizing predominantly M3 receptors and inhibit NSCLC cell growth, which suggest that M3 receptor antagonist might be a potential chemotherapeutic regimen for NSCLC.
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