ArticleCancer science2019
Conophylline suppresses pancreatic cancer desmoplasia and cancer-promoting cytokines produced by cancer-associated fibroblasts.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Cancer‑associated fibroblast‑derived extracellular vesicles promote pancreatic cancer progression via the RAP1B/ANLN axis.Oncology reports · 2026Article
- Discovery of Bisindoles that Activate Tumor-Associated Macrophages and Enhance Antitumor Immunity.ACS pharmacology & translational science · 2025Article
- Paracrine signaling in cancer-associated fibroblasts: central regulators of the tumor immune microenvironment.Journal of translational medicine · 2025Review
- Article
- Tumor-associated macrophages (TAMs): Constructing an immunosuppressive microenvironment bridge for pancreatic ductal adenocarcinoma (PDAC).Cancer pathogenesis and therapy · 2025Review
- Natural Compounds as Potential Therapeutics for Pancreatic Cancer: A Narrative Review.Current drug metabolism · 2025Review
- Article
- Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer.Cancer science · 2024Article
- Natural Compounds as Protease Inhibitors in Therapeutic Focus on Cancer Therapy.Anti-cancer agents in medicinal chemistry · 2024Review
- Role of Phytoconstituents in Cancer Treatment: A Review.Recent advances in food, nutrition & agriculture · 2024Review
- Spatial transcriptomics reveals the heterogeneity and FGG+CRP+ inflammatory cancer-associated fibroblasts replace islets in pancreatic ductal adenocarcinoma.Frontiers in oncology · 2023Article
- Potential of Compounds Originating from the Nature to Act in Hepatocellular Carcinoma Therapy by Targeting the Tumor Immunosuppressive Microenvironment: A Review.Molecules (Basel, Switzerland) · 2022Review
- Natural Products as Anticancer Agents: Current Status and Future Perspectives.Molecules (Basel, Switzerland) · 2022Review
- Natural Compounds Targeting Cancer-Associated Fibroblasts against Digestive System Tumor Progression: Therapeutic Insights.Biomedicines · 2022Review
- Cancer-associated fibroblasts promote tumor progression by lncRNA-mediated RUNX2/GDF10 signaling in oral squamous cell carcinoma.Molecular oncology · 2022Article
- Indole-Based Small Molecules as Potential Therapeutic Agents for the Treatment of Fibrosis.Frontiers in pharmacology · 2022Review
- Chemokine signaling in cancer-stroma communications.Journal of cell communication and signaling · 2021Review
- Tumor microenvironment: a prospective target of natural alkaloids for cancer treatment.Cancer cell international · 2021Review
- Review
- Targeting Fibrosis: The Bridge That Connects Pancreatitis and Pancreatic Cancer.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Despite recent advances in cancer treatment, pancreatic cancer is a highly malignant tumor type with a dismal prognosis and it is characterized by dense desmoplasia in the cancer tissue. Cancer-associated fibroblasts (CAF) are responsible for this fibrotic stroma and promote cancer progression. We previously reported that a novel natural compound conophylline (CnP) extracted from the leaves of a tropical plant reduced liver and pancreatic fibrosis by suppression of stellate cells. However, there have been no studies to investigate the effects of CnP on CAF, which is the aim of this work. Here, we showed that CAF stimulated indicators of pancreatic cancer malignancy, such as proliferation, invasiveness, and chemoresistance. We also showed that CnP suppressed CAF activity and proliferation, and inhibited the stimulating effects of CAF on pancreatic cancer cells. Moreover, CnP strongly decreased the various cytokines involved in cancer progression, such as interleukin (IL)-6, IL-8, C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand 12 (CXCL12), secreted by CAF. In vivo, CAF promoted tumor proliferation and desmoplastic formation in a mouse xenograft model, CnP reduced desmoplasia of tumors composed of pancreatic cancer cells + CAF, and combination therapy of CnP with gemcitabine remarkably inhibited tumor proliferation. Our findings suggest that CnP is a promising therapeutic strategy of combination therapy with anticancer drugs to overcome refractory pancreatic cancers.
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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.