ArticleCell biology and toxicology2021
Quercetin suppresses pancreatic ductal adenocarcinoma progression via inhibition of SHH and TGF-β/Smad signaling pathways.
Article in Cell biology and toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Research progress on antitumor effects of sea buckthorn, a traditional Chinese medicine homologous to food and medicine.Frontiers in nutrition · 2024Pooled it
- Phytochemicals as Multitarget Therapeutics in Pancreatic Cancer: Mechanisms, Clinical Evidence, and Translational Challenges.Phytotherapy research : PTR · 2026Review
- Quercetin suppresses the proliferation of thyroid cancer cells by reducing the expression level of DPP4 and inhibiting its enzyme activity.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Greater susceptibility of patients with idiopathic pulmonary fibrosis to basal cell carcinoma: a combined genomics and Mendelian randomization analysis.Translational cancer research · 2026Article
- Leveraging the molecular insights and therapeutic potential of diet-derived-flavonoids against pancreatic ductal adenocarcinoma.Frontiers in pharmacology · 2026Review
- Targeting TGF-βR1 Signaling Pathway in Pancreatic Cancer: A Potential Approach with Synthetic Flavanols.Anti-cancer agents in medicinal chemistry · 2026Article
- Enhancing Chemosensitivity With Quercetin: Mechanistic Insights Into MerTK and Associated Signaling Pathways.Cancer reports (Hoboken, N.J.) · 2025Review
- Inflammation, microbiota, and pancreatic cancer.Cancer cell international · 2025Review
- Therapeutical potential of natural products in treatment of pancreatic cancer: a review.Molecular biology reports · 2025Review
- Exploring the effects of quercetin-added pancreatic diet on metabolic homeostasis in dogs via metabolomics.PloS one · 2025Article
- Antitumor components and mechanisms ofFrontiers in pharmacology · 2025Review
- Research progress on the anti-cancer mechanisms of edible salty-flavored Chinese materia medica.Frontiers in pharmacology · 2025Review
- Quercetin and Nano-Derivatives: Potential and Challenges in Cancer Therapy.International journal of nanomedicine · 2025Review
- Botanical drugs and their natural compounds: a neglected treasury for inhibiting the carcinogenesis of pancreatic ductal adenocarcinoma.Pharmaceutical biology · 2024Review
- Smad4 regulates TGF-β1-mediated hedgehog activation to promote epithelial-to-mesenchymal transition in pancreatic cancer cells by suppressing Gli1 activity.Computational and structural biotechnology journal · 2024Article
- Determination of Biologically Active Compounds and Antioxidant Capacity In Vitro in Fruit of Small Cranberries (Antioxidants (Basel, Switzerland) · 2024Article
- Targeting the pancreatic tumor microenvironment by plant-derived products and their nanoformulations.Medical oncology (Northwood, London, England) · 2024Review
- A comprehensive review on phytochemicals in the treatment and prevention of pancreatic cancer: Focusing on their mechanism of action.Health science reports · 2024Article
- Molecular profile of metastasis, cell plasticity and EMT in pancreatic cancer: a pre-clinical connection to aggressiveness and drug resistance.Cancer metastasis reviews · 2024Review
- Suppression of TGF-β/Smad3 signaling pathway byIranian journal of basic medical sciences · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDA) is an aggressive type of malignant tumor with a poor prognosis and high mortality. Aberrant activation of hedgehog signaling plays a crucial role in the maintenance and progression of PDA. Here, we report that the dietary bioflavonoid quercetin has therapeutic potential for PDA by targeting sonic hedgehog (SHH) signaling. The effects of quercetin on the proliferation, apoptosis, migration, and invasion of pancreatic cancer cells (PCCs) and tumor growth and metastasis in PDA xenograft mouse models were evaluated. Additionally, SHH signaling activity was determined. Quercetin significantly inhibited PCC proliferation by downregulating c-Myc expression. In addition, quercetin suppressed epithelial-mesenchymal transition (EMT) by reducing TGF-β1 level, which resulted in inhibition of PCC migration and invasion. Moreover, quercetin induced PCC apoptosis through mitochondrial and death receptor pathways. In nude mouse models, PDA growth and metastasis were reduced by quercetin treatment. Mechanically, quercetin exerts its therapeutic effects on PDA by decreasing SHH activity. Interestingly, quercetin-induced SHH inactivation is mainly dependent on Gli2, but not Gli1. Enhance SHH activity by recombinant Shh protein abolished the quercetin-mediated inhibition of PCC proliferation, migration, and invasion. Furthermore, Shh activated TGF-β1/Smad2/3 signaling and promoted EMT by inducing the expression of Zeb2 and Snail1 that eventually resulted in a partial reversal of quercetin-mediated inhibition of PCC migration and invasion. We conclude that quercetin inhibited the growth, migration, and invasion and induced apoptosis of PCCs by antagonizing SHH and TGF-β/Smad signaling pathways. Thus, quercetin may be a potential candidate for PDA treatment.
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