ArticlePloS one2014
The polyphenols (-)-epigallocatechin-3-gallate and luteolin synergistically inhibit TGF-β-induced myofibroblast phenotypes through RhoA and ERK inhibition.
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 23 papers.
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Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- Jaboticaba peel extract limits castration-resistant prostate cancer aggressiveness by counteracting EMT through steroid hormone and TGF-β signaling modulation.Journal of molecular histology · 2026Article
- Interactions of flavonoid and coumarin derivative compounds with transforming growth factor-beta receptor 1 (TGF-βR1): integrating virtual screening, molecular dynamics, maximum common substructure, and ADMET approaches in the treatment of idiopathic pulmonary fibrosis.Journal of molecular modeling · 2025Article
- The C-X-C Motif Chemokine Ligand 5, Which Exerts an Antioxidant Role by Inducing HO-1 Expression, Is C-X-C Motif Chemokine Receptor 2-Dependent in Human Prostate Stroma and Cancer Cells.Antioxidants (Basel, Switzerland) · 2024Article
- The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy.Frontiers in immunology · 2024Review
- Therapeutic Potential of Luteolin on Cancer.Vaccines · 2023Review
- Targeting extracellular matrix through phytochemicals: a promising approach of multi-step actions on the treatment and prevention of cancer.Frontiers in pharmacology · 2023Review
- Heterotypic signaling of cancer-associated fibroblasts in shaping the cancer cell drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Polyphenon E Effects on Gene Expression in PC-3 Prostate Cancer Cells.International journal of molecular sciences · 2022Article
- Luteolin, a Potent Anticancer Compound: From Chemistry to Cellular Interactions and Synergetic Perspectives.Cancers · 2022Review
- Standardization of the ethanolic extract of Crinum latifolium leaves by two bioactive markers with antiproliferative activity against TGF-β-promoted prostate stromal cells (WPMY-1).BMC complementary medicine and therapies · 2022Article
- Histological Evidence of Wound Healing Improvement in Rats Treated with Oral Administration of Hydroalcoholic Extract ofCurrent issues in molecular biology · 2021Article
- Luteolin and cancer metastasis suppression: focus on the role of epithelial to mesenchymal transition.Medical oncology (Northwood, London, England) · 2021Review
- Molecular Insights into the Multifunctional Role of Natural Compounds: Autophagy Modulation and Cancer Prevention.Biomedicines · 2020Review
- Article
- Natural products remodel cancer-associated fibroblasts in desmoplastic tumors.Acta pharmaceutica Sinica. B · 2020Review
- Article
- Phyto-polyphenols as potential inhibitors of breast cancer metastasis.Molecular medicine (Cambridge, Mass.) · 2018Review
- Cancer Chemoprevention by Phytochemicals: Nature's Healing Touch.Molecules (Basel, Switzerland) · 2017Review
- The roles of epigallocatechin-3-gallate in the treatment of neuropathic pain: an update on preclinical in vivo studies and future perspectives.Drug design, development and therapy · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The presence of reactive stroma, predominantly composed of myofibroblasts, is directly associated with and drives prostate cancer progression. We have previously shown that (-)-Epigallocatechin-3-gallate (EGCG), in the form of Polyphenon E, significantly decreases serum levels of HGF and VEGF in prostate cancer patients. Given that HGF and VEGF are secreted from surrounding tumor myofibroblasts, these observations suggested that EGCG may inhibit prostate cancer-associated myofibroblast differentiation. Herein, we demonstrate that micromolar combinations of EGCG and a second polyphenol, luteolin, synergistically inhibit TGF-β-induced myofibroblast phenotypes in prostate fibroblast cell lines, as observed primarily by potentiation of fibronectin expression. Functionally, EGCG and luteolin inhibited TGF-β-induced extracellular matrix contraction, an enhancer of tumor cell invasion. EGCG and luteolin inhibited downstream TGF-β-induced signaling, including activation of ERK and AKT, respectively, but mechanistically, only ERK appeared to be necessary for TGF-β-induced fibronectin expression. Furthermore, neither EGCG nor luteolin affected Smad signaling or nuclear translocation. Rho signaling was found to be necessary for TGF-β-induced fibronectin expression and EGCG and luteolin each reduced RhoA activation. Finally, EGCG and luteolin were shown to reverse TGF-β-induced fibronectin expression, implicating that these natural compounds may be useful not only in preventing but also in treating already activated myofibroblasts and the diseases they cause, including cancer. The ability of EGCG and luteolin to synergistically target myofibroblasts suggests that combined clinical use of these compounds could prevent or reverse cancer progression through targeting the tumor microenvironment, in addition to the tumor itself.
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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.