ArticleBiomolecules2019
YAP Inhibition by Nuciferine via AMPK-Mediated Downregulation of HMGCR Sensitizes Pancreatic Cancer Cells to Gemcitabine.
Article in Biomolecules, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Aporphine AlkaloidPharmaceuticals (Basel, Switzerland) · 2026Article
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- Insights into nuciferine: A natural multifunctional bioactive alkaloid (Review).Molecular medicine reports · 2026Review
- Therapeutic efficacy of canagliflozin against hepatocarcinogenesis induced by CDD/DEN/TAA in a rat model: regulation of AMPK/HIF-1α/YAP-1/TAZ signaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Natural aporphine alkaloids: A comprehensive review of phytochemistry, pharmacokinetics, anticancer activities, and clinical application.Journal of advanced research · 2024Review
- Value of diffusion kurtosis MR imaging and conventional diffusion weighed imaging for evaluating response to first-line chemotherapy in unresectable pancreatic cancer.Cancer imaging : the official publication of the International Cancer Imaging Society · 2024Article
- Nuciferine induces autophagy to relieve vascular cell adhesion molecule 1 activation via repressing the Akt/mTOR/AP1 signal pathway in the vascular endothelium.Frontiers in pharmacology · 2023Article
- Lipid metabolism in pancreatic cancer: emerging roles and potential targets.Cancer communications (London, England) · 2022Review
- Role of hypoxia in the tumor microenvironment and targeted therapy.Frontiers in oncology · 2022Review
- Article
- Natural Aporphine Alkaloids with Potential to Impact Metabolic Syndrome.Molecules (Basel, Switzerland) · 2021Review
- Review
- From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues.Biomolecules · 2021Review
- UPLC-Q-TOF/MS-Based Serum Metabolomics Reveals the Anti-Ischemic Stroke Mechanism of Nuciferine in MCAO Rats.ACS omega · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuciferine, a major aporphine alkaloid constituent of lotus leaves, is a raw material for obesity treatment. Extensive studies have revealed that obesity is associated with pancreatic cancer (PC). However, it has not been clarified whether nuciferine could be used in PC treatment or prevention. Here, we show that nuciferine could enhance the sensitivity of PC cells to gemcitabine in both cultured cells and the xenograft mouse model. The mechanism study demonstrated that nuciferine induced YAP Ser127 phosphorylation [pYAP(Ser127)] through AMPK-mediated 3-hydroxy-3-methyl-glutaryl-coA reductase (HMGCR) downregulation. Remarkably, wild-type YAP overexpression or YAP Ser127 mutant could resist to nuciferine and no longer sensitize PC cells to gemcitabine. Knockdown of AMPK attenuated pYAP(Ser127) induced by nuciferine. Moreover, knockdown of AMPK reversed nuciferine-mediated HMGCR downregulation. Notably, HMGCR inhibiting could restrain YAP by phosphorylation Ser 127, and therefore enhance the efficiency of gemcitabine in PC cells. In line with this consistent, overexpression of HMGCR reduced growth inhibition caused by nuciferine and/or gemcitabine treatment in PC cells. In summary, these results provide an effective supplementary agent and suggest a therapeutic strategy to reduce gemcitabine resistance in PC.
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