ArticleCell death & disease2024
Prosapogenin A induces GSDME-dependent pyroptosis of anaplastic thyroid cancer through vacuolar ATPase activation-mediated lysosomal over-acidification.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- [Network pharmacology-based investigation of the therapeutic efficacy and molecular targets of Xiangsha Liujunzi decoction in thyroid carcinoma].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
- [Inhibitory effect of lonafarnib on anaplastic thyroid carcinoma cells and xenograft tumor growth in nude mice].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
- Direct coupling and protective activation of DRP1 by the DNA-PKcs inhibitor KU-57788 synergizes with ferroptosis in anaplastic thyroid cancer cells.Cell death & disease · 2026Article
- Intestinal epithelial AhR deletion aggravates DSS-induced colitis via lipid- and amino-acid metabolic reprogramming: integrated metabolomic-transcriptomic evidence.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Triptolide in Combination with the Gli1 Inhibitor GANT61 Eradicates Anaplastic Thyroid Cancer by Suppressing Cancer Stem Cell Self-Renewal and Enhancing Apoptosis and Pyroptosis.International journal of biological sciences · 2026Article
- Isobavachalcone induces concurrent apoptosis and pyroptosis in anaplastic thyroid cancer cells by modulating the caspase-mediated cleavage of PARP and GSDME.American journal of cancer research · 2026Article
- Organelles and cancer cell pyroptosis: overview and perspectives.Cell death & disease · 2025Review
- Melatonin Supplementation Relieves Fluoride-Induced Bone Injury via Ion Homeostasis Disorder and PINK1/Parkin-Mediated Mitophagy.Foods (Basel, Switzerland) · 2025Article
- Gasdermins: multifunctional effectors of membrane permeabilization across cellular compartments.The FEBS journal · 2025Review
- Lysosomal homeostasis regulates myocardial ischemia-reperfusion injury through autophagy pathway.Scientific reports · 2025Article
- From mechanisms to markers: role of pyroptosis in revolutionizing thyroid cancer care.Cell death discovery · 2025Review
- The Emerging Roles of Vacuolar-Type ATPase-Dependent Lysosomal Acidification in Cardiovascular Disease.Biomolecules · 2025Review
- Erianin induces apoptosis and pyroptosis via MAPK/ERK and PI3K/Akt pathways and synergizes with anlotinib in anaplastic thyroid carcinoma.Frontiers in pharmacology · 2025Article
- Targeted photodynamic therapy: enhancing efficacy through specific organelle engagement.Frontiers in pharmacology · 2025Review
- Development and Verification of Diagnosis Model for Papillary Thyroid Cancer Based on Pyroptosis-Related Genes: A Bioinformatic and in vitro Investigation.Journal of inflammation research · 2024Article
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20 authors.
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Abstract
Anaplastic thyroid cancer (ATC) is among the most aggressive and metastatic malignancies, often resulting in fatal outcomes due to the lack of effective treatments. Prosapogenin A (PA), a bioactive compound prevalent in traditional Chinese herbs, has shown potential as an antineoplastic agent against various human tumors. However, its effects on ATC and the underlying mechanism remain unclear. Here, we demonstrate that PA exhibits significant anti-ATC activity both in vitro and in vivo by inducing GSDME-dependent pyroptosis in ATC cells. Mechanistically, PA promotes lysosomal membrane permeabilization (LMP), leading to the release of cathepsins that activate caspase 8/3 to cleave GSDME. Remarkably, PA significantly upregulates three key functional subunits of V-ATPase-ATP6V1A, ATP6V1B2, and ATP6V0C-resulting in lysosomal over-acidification. This over-acidification exacerbates LMP and subsequent lysosomal damage. Neutralization of lysosomal lumen acidification or inhibition/knockdown of these V-ATPase subunits attenuates PA-induced lysosomal damage, pyroptosis and growth inhibition of ATC cells, highlighting the critical role for lysosomal acidification and LMP in PA's anticancer effects. In summary, our findings uncover a novel link between PA and lysosomal damage-dependent pyroptosis in cancer cells. PA may act as a V-ATPase agonist targeting lysosomal acidification, presenting a new potential therapeutic option for ATC treatment.
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