ArticlePloS one2014
Curcumin suppresses crosstalk between colon cancer stem cells and stromal fibroblasts in the tumor microenvironment: potential role of EMT.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 143 citations in OpenAlex.
- Emerging agents that target signaling pathways in cancer fibroblast cells (Review).International journal of oncology · 2026Review
- The anti-migratory effect of curcumin in colorectal cancer involves IKKβ/NF-κB/Snail-mediated EMT inhibition.Translational cancer research · 2026Article
- Mechanistic insights into polyphenolic constituents from traditional Chinese medicines in inhibiting colorectal cancer metastasis.Natural products and bioprospecting · 2026Review
- Advances of curcumin-loaded hydrogels for multimodal cancer therapeutics.Discover oncology · 2026Review
- The role of the tumor microenvironment in drug resistance acquisition in lung squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2026Review
- Smart nanoparticle delivery systems for curcumin: a targeted strategy to enhance anticancer efficacy and bioavailability.Journal of materials science. Materials in medicine · 2026Review
- Antitumor Activity of All-Trans Retinoic Acid and Curcumin-Loaded BSA Nanoparticles Against U87 Glioblastoma Cells.Life (Basel, Switzerland) · 2026Article
- Body mass index-defined overweight (but not obese) correlates with better postoperative prognosis in colorectal cancer.Journal of gastrointestinal oncology · 2025Article
- Tumor infiltration therapy: from FDA approval to next-generation approaches.Clinical and experimental medicine · 2025Review
- Paracrine signaling in cancer-associated fibroblasts: central regulators of the tumor immune microenvironment.Journal of translational medicine · 2025Review
- Polyphenol Intake in Elderly Patients: A Novel Approach to Counteract Colorectal Cancer Risk?International journal of molecular sciences · 2025Review
- Natural Alternatives in the Treatment of Colorectal Cancer: A Mechanisms Perspective.Biomolecules · 2025Review
- A comprehensive update on the potential of curcumin to enhance chemosensitivity in colorectal cancer.Pharmacological reports : PR · 2025Review
- Resveratrol and p53: How are they involved in CRC plasticity and apoptosis?Journal of advanced research · 2024Review
- B7-H3 at the crossroads between tumor plasticity and colorectal cancer progression: a potential target for therapeutic intervention.Cancer metastasis reviews · 2024Review
- Role of tumor microenvironment in cancer progression and therapeutic strategy.Cancer medicine · 2023Review
- Laparoscopic-Assisted Colorectal Resection Can Reduce the Inhibition of Immune Function Compared with Conventional Open Surgery: A Retrospective Clinical Study.Journal of clinical medicine · 2023Article
- Colorectal Cancer Bioengineered Microtissues as a Model to Replicate Tumor-ECM Crosstalk and Assess Drug Delivery Systems In Vitro.International journal of molecular sciences · 2023Article
- 7Marine drugs · 2023Article
- Cancer Stem Cell Formation Induced and Regulated by Extracellular ATP and Stanniocalcin-1 in Human Lung Cancer Cells and Tumors.International journal of molecular sciences · 2022Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveInteraction of stromal and tumor cells plays a dynamic role in initiating and enhancing carcinogenesis. In this study, we investigated the crosstalk between colorectal cancer (CRC) cells with stromal fibroblasts and the anti-cancer effects of curcumin and 5-Fluorouracil (5-FU), especially on cancer stem cell (CSC) survival in a 3D-co-culture model that mimics in vivo tumor microenvironment.
methodsColon carcinoma cells HCT116 and MRC-5 fibroblasts were co-cultured in a monolayer or high density tumor microenvironment model in vitro with/without curcumin and/or 5-FU.
resultsMonolayer tumor microenvironment co-cultures supported intensive crosstalk between cancer cells and fibroblasts and enhanced up-regulation of metastatic active adhesion molecules (β1-integrin, ICAM-1), transforming growth factor-β signaling molecules (TGF-β3, p-Smad2), proliferation associated proteins (cyclin D1, Ki-67) and epithelial-to-mesenchymal transition (EMT) factor (vimentin) in HCT116 compared with tumor mono-cultures. High density tumor microenvironment co-cultures synergistically increased tumor-promoting factors (NF-κB, MMP-13), TGF-β3, favored CSC survival (characterized by up-regulation of CD133, CD44, ALDH1) and EMT-factors (increased vimentin and Slug, decreased E-cadherin) in HCT116 compared with high density HCT116 mono-cultures. Interestingly, this synergistic crosstalk was even more pronounced in the presence of 5-FU, but dramatically decreased in the presence of curcumin, inducing biochemical changes to mesenchymal-epithelial transition (MET), thereby sensitizing CSCs to 5-FU treatment.
conclusionEnrichment of CSCs, remarkable activation of tumor-promoting factors and EMT in high density co-culture highlights that the crosstalk in the tumor microenvironment plays an essential role in tumor development and progression, and this interaction appears to be mediated at least in part by TGF-β and EMT. Modulation of this synergistic crosstalk by curcumin might be a potential therapy for CRC and suppress metastasis.
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