ArticleOncotarget2016
IRE1α inhibition by natural compound genipin on tumour associated macrophages reduces growth of hepatocellular carcinoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Biological impact and therapeutic implication of tumor-associated macrophages in hepatocellular carcinoma.Cell death & disease · 2024Review
- Genipin's potential as an anti-cancer agent: from phytochemical origins to clinical prospects.Medical oncology (Northwood, London, England) · 2024Review
- The role of tumor-associated macrophages in hepatocellular carcinoma progression: A narrative review.Cancer medicine · 2023Review
- Genipin-activating PPARγ impedes CCR2-mediated macrophage infiltration into postoperative liver to suppress recurrence of hepatocellular carcinoma.International journal of biological sciences · 2023Article
- Plant-derived natural products and combination therapy in liver cancer.Frontiers in oncology · 2023Review
- 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
- UCP2 as a Cancer Target through Energy Metabolism and Oxidative Stress Control.International journal of molecular sciences · 2022Review
- The Endoplasmic Reticulum Stress Sensor IRE1α Regulates the UV DNA Repair Response through the Control of Intracellular Calcium Homeostasis.The Journal of investigative dermatology · 2022Article
- Genipin, an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature.International journal of molecular sciences · 2022Review
- Tumor-Associated Macrophages in Hepatocellular Carcinoma Pathogenesis, Prognosis and Therapy.Cancers · 2022Review
- The Role of Natural Products in Treatment of Depressive Disorder.Current neuropharmacology · 2022Article
- Collagen XV Promotes ER Stress-Induced Inflammation through Activating Integrin β1/FAK Signaling Pathway and M1 Macrophage Polarization in Adipose Tissue.International journal of molecular sciences · 2021Article
- Impact of Digestive Inflammatory Environment and Genipin Crosslinking on Immunomodulatory Capacity of Injectable Musculoskeletal Tissue Scaffold.International journal of molecular sciences · 2021Article
- Direct inhibition of the TLR4/MyD88 pathway by geniposide suppresses HIF-1α-independent VEGF expression and angiogenesis in hepatocellular carcinoma.British journal of pharmacology · 2020Article
- Targeting tumour microenvironment by tyrosine kinase inhibitor.Molecular cancer · 2018Review
- Genipin normalizes depression-like behavior induced by prenatal stress through inhibiting DNMT1.Epigenetics · 2018Article
- Identification of WT1 as determinant of heptatocellular carcinoma and its inhibition by Chinese herbal medicineOncotarget · 2017Article
- Thrombospondin-1 Production Regulates the Inflammatory Cytokine Secretion in THP-1 Cells Through NF-κB Signaling Pathway.Inflammation · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidences postulated the influential roles of macrophages in mediating hepatocellular carcinoma (HCC) initiation and progression. In this study, we demonstrate that a small molecule, genipin reduced HCC growth through suppressing IRE1α-mediated infiltration and priming of tumour associated macrophages (TAMs). Oral administration of genipin (30mg/kg/2days) suppressed orthotopic HCC tumour growth without challenging the viability and proliferation of HCC cells. Genipin reduced infiltration of inflammatory monocytes into liver and tumour thereby suppressed TAMs presence in HCC microenvironment. Suppression of HCC growth was diminished in HCC-implanted mice with depletion of TAMs by liposome clodronate. Genipin inhibited the TAMs migration, and reduced expression of TAMs-derived inflammatory cytokines that favors HCC proliferation. This is revealed by the in vivo deletion of IRE1α on TAMs in genipin-treated HCC-implanted mice. Diminishing IRE1α neutralised the inhibitory effect of genipin on TAMs. Silencing the expression of IRE1α greatly reduced TAMs migration and expression of inflammatory cytokines that prime HCC proliferation. Suppression of IRE1α led to reduced XBP-1 splicing and NF-κB activation. The reduced association of IRE1α with TRAF2 and IKK complex may be responsible for the genipin-mediated inactivation of NF-κB. The findings show the important role of TAMs in inhibitory effect of genipin on HCC, and TAMs-expressing IRE1α as a promising target for disrupting the tumour environment that favor of HCC development.
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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.