ArticleChinese medicine2022
Nitidine chloride induces caspase 3/GSDME-dependent pyroptosis by inhibting PI3K/Akt pathway in lung cancer.
Article in Chinese medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Development of Immunoelectron Microscopy for VASN Detection Using Multiple Models and Identification of VASN as a Key Regulator of Mitochondrial Homeostasis in Hepatocellular Carcinoma Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- KLF1 Exerts Pro-Tumour Role in Liver Cancer via Inhibiting ACSL4/LPCAT3-Regulated Ferroptosis.Journal of cellular and molecular medicine · 2026Article
- p53 Orchestrates the Immunogenic-Tolerogenic Pyroptosis Switch in Non-Small Cell Lung Cancer: A Systems Biology Approach.Computational and structural biotechnology journal · 2026Article
- PI3K/mTOR Inhibitor Induces Context-Dependent Apoptosis and Methuosis in Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Pyroptosis in cancer therapy: a double-edged sword for immune activation and tumor progression.Molecular cancer · 2025Review
- Target discovery-directed pharmacological mechanism elucidation of bioactive natural products.Medical review (2021) · 2025Review
- Is pyroptosis a brake or an accelerator in the fate of the tumor?Cell death & disease · 2025Review
- Nitidine chloride may mediate its antitumor effects by targeting kinesin family member 20A in colorectal cancer cells.World journal of clinical oncology · 2025Article
- Article
- TEAD4-mediated upregulation of LPAR3 augments hepatic stellate cell activation in portal hypertension.Cell biology and toxicology · 2025Article
- Cranberry Extract Ameliorates Diabetic Cognitive Impairment in Rats Via LncRNA GAS-5 Downregulation and Pyroptosis Pathway Inhibition.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Kinesin family member 14 expression and its clinical implications in colorectal cancer.World journal of gastrointestinal oncology · 2025Article
- A novel approach to glioblastoma multiforme treatment using modulation of key pathways by naturally occurring small molecules.Inflammopharmacology · 2025Review
- GSDME in cardiovascular diseases: research system and contemporary progress.Frontiers in immunology · 2025Review
- Ferroptosis: a novel pharmacological mechanism against multiple myeloma.Frontiers in pharmacology · 2025Review
- Eupalinolide A inhibits cancer progression and induces ferroptosis and apoptosis by targeting the AMPK/mTOR/SCD1 signalling in non-small cell lung cancer.Frontiers in pharmacology · 2025Article
- SIRT1 Inhibition-Induced Mitochondrial Damage Promotes GSDME-Dependent Pyroptosis in Hepatocellular Carcinoma Cells.Molecular biotechnology · 2024Article
- Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication.Molecular cancer · 2024Review
- Pyroptosis in health and disease: mechanisms, regulation and clinical perspective.Signal transduction and targeted therapy · 2024Review
- Paraptosis: a non-classical paradigm of cell death for cancer therapy.Acta pharmacologica Sinica · 2024Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAs the increasing mortality and incidence of lung cancer (LC), there is an urgent need to discover novel treatment agent. In this study, we aimed to investigate the anti-LC effects of nitidine chloride (NC), a small molecular compound extracted from Chinese herbal medicine, while detailing its underlying mechanisms.
methodsCell viability was detected by MTT assays and five cell death inhibitors, including ferrostatin-1 (Fer-1), Z-VAD-FMK, necrostatin-1 (Nec-1), disulfiram (DSF) and IM-54 were used to explore the type of cell death induced by NC. The microscopic features of NC-induced pyroptosis were assessed by transmission electron microscopy (TEM) and the pyroptotic-related proteins such as caspase and gasdermin family, were examined by western blot. Network pharmacology was employed to predict the potential mechanisms of NC in lung cancer treatment. CETSA and DARTs were used to determine the activity of NC binding to targeted protein. Xenograft mice model was established to further investigate the inhibitory effect and mechanism of NC against LC.
resultsThe pyroptosis inhibitor (DSF) and apoptosis inhibitor (Z-VAD-FMK) but not IM-54, necrostatin-1, or Ferrostatin-1 rescued NC-induced cell death. Morphologically, H1688 and A549 cells treated with NC showed notably pyroptotic features, such as cell swelling and large bubbles emerging from the plasma membrane. Gasdermin E (GSDME) rather than GSDMC or GSDMD was cleaved in NC-treated H1688 and A549 cells with an increased cleavage of caspase 3. Combined with network pharmacology and molecule docking, PI3K/Akt signaling axis was predicted and was further verified by CETSA and DARTs assay. In addition, the activation of PI3K is able to rescue the pyroptosis induced by NC in vitro. In xenograft model of LC, NC significantly hindered the transduction of PI3K-AKT pathway, inducing pyroptosis of tumor.
conclusionOur data indicated that NC is a potential therapeutic agent for the treatment of LC via triggering GSDME-dependent pyroptosis.
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