ArticleCell death & disease2018
Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3β pathway in human lung cancer cells.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses 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
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Hydroxysafflor yellow A for ischemic heart diseases: a systematic review and meta-analysis of animal experiments.Frontiers in pharmacology · 2025Pooled it
- Hirsutine, an Emerging Natural Product with Promising Therapeutic Benefits: A Systematic Review.Molecules (Basel, Switzerland) · 2023Pooled it
- Hirsutine mitigates high glucose-induced cell injuryRenal failure · 2026Article
- Harnessing GSK-3β inhibition for lung cancer therapy: emerging opportunities and challenges.Medical oncology (Northwood, London, England) · 2025Review
- ROCK inhibition suppresses glioblastoma via a PTEN-associated reduction in PI3K/AKT signaling.Medical oncology (Northwood, London, England) · 2025Article
- Effects of HTLV-1 on leukocyte trafficking and migration in ACs compared to healthy individuals.BMC research notes · 2024Article
- EFHD1 promotes osteosarcoma proliferation and drug resistance by inhibiting the opening of the mitochondrial membrane permeability transition pore (mPTP) by binding to ANT3.Cellular and molecular life sciences : CMLS · 2024Article
- Mitochondrial carrier homolog 2 increases malignant phenotype of human gastric epithelial cells and promotes proliferation, invasion, and migration of gastric cancer cells.World journal of gastrointestinal oncology · 2024Article
- Comprehensive transcriptomic analysis identifies SLC25A4 as a key predictor of prognosis in osteosarcoma.Frontiers in genetics · 2024Article
- Inhibitory effect and mechanism of hirsuteine on NCI‑H1299 lung cancer cell lines.Oncology letters · 2023Article
- Metformin reverses oxidative stress‑induced mitochondrial dysfunction in pre‑osteoblasts via the EGFR/GSK‑3β/calcium pathway.International journal of molecular medicine · 2023Article
- Promising Strategy of mPTP Modulation in Cancer Therapy: An Emerging Progress and Future Insight.International journal of molecular sciences · 2023Review
- Bioactive PI3-kinase/Akt/mTOR Inhibitors in Targeted Lung Cancer Therapy.Advanced pharmaceutical bulletin · 2023Review
- The mechanisms of action of mitochondrial targeting agents in cancer: inhibiting oxidative phosphorylation and inducing apoptosis.Frontiers in pharmacology · 2023Review
- Effects of hirsuteine on MDA-MB-453 breast cancer cell proliferation.Oncology letters · 2023Article
- Dual efficacy of Fasudil at improvement of survival and reinnervation of flap through RhoA/ROCK/PI3K/Akt pathway.International wound journal · 2022Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- BRAF V600E protect from cell death via inhibition of the mitochondrial permeability transition in papillary and anaplastic thyroid cancers.Journal of cellular and molecular medicine · 2022Article
- rAAV-delivered PTEN therapeutics for prostate cancer.Molecular therapy. Nucleic acids · 2022Article
- Inhibition of the PINK1-Parkin Pathway Enhances the Lethality of Sorafenib and Regorafenib in Hepatocellular Carcinoma.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hirsutine extracted from Uncaria rhynchophylla has been shown to exhibit anti-cancer activity. However, the molecular mechanism by which hirsutine exhibits anti-lung cancer activity remains unclear. In the present study, we showed that hirsutine induces apoptosis in human lung cancer cells via loss of mitochondrial membrane potential (∆ψm), adenosine triphosphate (ATP) depletion, ROS production, as well as cytochrome c release. Dephosphorylation of GSK3β is involved in hirsutine-mediated mitochondrial permeability transition pore (mPTP) opening through ANT1/CypD interaction. Mechanistic study revealed that interruption of ROCK1/PTEN/PI3K/Akt signaling pathway plays a critical role in hirsutine-mediated GSK3β dephosphorylation and mitochondrial apoptosis. Our in vivo study also showed that hirsutine effectively inhibits tumor growth in a A549 xenograft mouse model through ROCK1/PTEN/PI3K/Akt signaling-mediated GSK3β dephosphorylation and apoptosis. Collectively, these findings suggest a hierarchical model in which induction of apoptosis by hirsutine stems primarily from activation of ROCK1 and PTEN, inactivation of PI3K/Akt, leading in turn to GSK3β dephosphorylation and mPTP opening, and culminating in caspase-3 activation and apoptosis. These findings could provide a novel mechanistic basis for the application of hirsutine in the treatment of human lung cancer.
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