ArticleScientific reports2017
Inhibition of hypoxic response decreases stemness and reduces tumorigenic signaling due to impaired assembly of HIF1 transcription complex in pancreatic cancer.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis 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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Size-Transformable Nanoparticles for Tumor Drug Delivery: Distinct Roles of Shrinkage, Enlargement, and Reassembly.Biomedicines · 2026Review
- Targeting CIC::DUX4 sarcoma with Minnelide in a dual recombinase-initiated genetically engineered mouse model.The Journal of clinical investigation · 2026Article
- Triptolide: A Narrative Review of Its Traditional Use, Derivatives, Pharmacology, Antitumor Effect, and Clinical Applications.Cancers · 2026Review
- The RASSF1C-HIF-1α axis drives macrophage lipid metabolism to promote pancreatic cancer.Cell death & disease · 2026Article
- HIF1α mediates resistance to radiation and to KRAS inhibitors in pancreatic adenocarcinoma.PloS one · 2026Article
- Niclosamide nanoparticles enhance pancreatic cancer sensitivity to gemcitabine via HIF-1α inhibition.iScience · 2025Article
- Efficacy of Minnelide in a Next-Generation Dual-Recombinase Regulated Genetically Engineered Mouse Model of CIC::DUX4 Sarcoma.bioRxiv : the preprint server for biology · 2025Article
- Pharmacological, computational, and mechanistic insights into triptolide's role in targeting drug-resistant cancers.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- [Research Advances in the Roles of High-Altitude Hypoxic Stress in Hepatocellular Carcinoma].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Review
- Triptolide and its prodrug Minnelide target high-risk MYC-amplified medulloblastoma in preclinical models.The Journal of clinical investigation · 2024Article
- AI identifies potent inducers of breast cancer stem cell differentiation based on adversarial learning from gene expression data.Briefings in bioinformatics · 2024Article
- Therapeutic Targeting of Hypoxia-Inducible Factors in Cancer.International journal of molecular sciences · 2024Review
- Cancer Metabolism under Limiting Oxygen Conditions.Cold Spring Harbor perspectives in medicine · 2024Review
- Lauric Acid Overcomes Hypoxia-Induced Gemcitabine Chemoresistance in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2023Article
- The Extracellular Matrix: A Key Accomplice of Cancer Stem Cell Migration, Metastasis Formation, and Drug Resistance in PDAC.Cancers · 2022Review
- Review
- Review
- A potential signaling axis between RON kinase receptor and hypoxia-inducible factor-1 alpha in pancreatic cancer.Molecular carcinogenesis · 2021Article
- Hypoxia-Driven Oncometabolite L-2HG Maintains Stemness-Differentiation Balance and Facilitates Immune Evasion in Pancreatic Cancer.Cancer research · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Pancreatic tumors are renowned for their extremely hypoxic centers, resulting in upregulation of a number of hypoxia mediated signaling pathways including cell proliferation, metabolism and cell survival. Previous studies from our laboratory have shown that Minnelide, a water-soluble pro-drug of triptolide (anti-cancer compound), decreases viability of cancer cells in vitro as well as in vivo. However, its mechanism of action remain elusive. In the current study we evaluated the effect of Minnelide, on hypoxia mediated oncogenic signaling as well as stemness in pancreatic cancer. Minnelide has just completed Phase 1 trial against GI cancers and is currently awaiting Phase 2 trials. Our results showed that upon treatment with triptolide, HIF-1α protein accumulated in pancreatic cancer cells even though hypoxic response was decreased in them. Our studies showed even though HIF-1α is accumulated in the treated cells, there was no decrease in HIF-1 binding to hypoxia response elements. However, the HIF-1 transcriptional activity was significantly reduced owing to depletion of co-activator p300 upon treatment with triptolide. Further, treatment with triptolide resulted in a decreased activity of Sp1 and NF-kB the two major oncogenic signaling pathway in pancreatic cancer along with a decreased tumor initiating cell (TIC) population in pancreatic tumor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.