ArticleCarcinogenesis2016
Beneficial effects of the naturally occurring flavonoid silibinin on the prostate cancer microenvironment: role of monocyte chemotactic protein-1 and immune cell recruitment.
Article in Carcinogenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy.Frontiers in oncology · 2022Pooled it
- Emerging agents that target signaling pathways in cancer fibroblast cells (Review).International journal of oncology · 2026Review
- Rapid Human Skin Barrier Disruption by Sodium Dodecyl Sulfate and Associated Molecular Mechanisms.Allergy · 2026Article
- 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
- Silibinin Anticancer Effects Through the Modulation of the Tumor Immune Microenvironment in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Paracrine signaling in cancer-associated fibroblasts: central regulators of the tumor immune microenvironment.Journal of translational medicine · 2025Review
- Therapeutic potential and mechanistic insights of silibinin targeting cancer-associated fibroblasts in colorectal cancer.Frontiers in pharmacology · 2025Article
- Chemokine ligand 2: beyond chemotaxis-a multifaceted role in tumor progression.Frontiers in immunology · 2025Review
- Current Understanding of Flavonoids in Cancer Therapy and Prevention.Metabolites · 2023Review
- Targeting extracellular matrix through phytochemicals: a promising approach of multi-step actions on the treatment and prevention of cancer.Frontiers in pharmacology · 2023Review
- Flavonoids against non-physiologic inflammation attributed to cancer initiation, development, and progression-3PM pathways.The EPMA journal · 2021Review
- Targeting phytoprotection in the COVID-19-induced lung damage and associated systemic effects-the evidence-based 3PM proposition to mitigate individual risks.The EPMA journal · 2021Review
- Identification of key genes in the tumor microenvironment of lung adenocarcinoma.Medical oncology (Northwood, London, England) · 2021Article
- Immune Checkpoint Inhibitors: A Promising Treatment Option for Metastatic Castration-Resistant Prostate Cancer?International journal of molecular sciences · 2021Review
- Proteomics reveals the function reverse of MPSSS-treated prostate cancer-associated fibroblasts to suppress PC-3 cell viability via the FoxO pathway.Cancer medicine · 2021Article
- Molecular Basis of Prostate Cancer and Natural Products as Potential Chemotherapeutic and Chemopreventive Agents.Frontiers in pharmacology · 2021Review
- Natural products remodel cancer-associated fibroblasts in desmoplastic tumors.Acta pharmaceutica Sinica. B · 2020Review
- Nanomedicines modulating tumor immunosuppressive cells to enhance cancer immunotherapy.Acta pharmaceutica Sinica. B · 2020Review
- Silibinin inhibits epithelial‑mesenchymal transition of renal cell carcinoma through autophagy‑dependent Wnt/β‑catenin signaling.International journal of molecular medicine · 2020Article
- Crosstalk between cancer-associated fibroblasts and immune cells in cancer.Journal of cellular and molecular medicine · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor microenvironment plays an essential role in prostate carcinogenesis and offers novel opportunities to prevent and treat prostate cancer (PCA). Here, we investigated the ability of cancer-associated fibroblasts (CAFs) to promote PCA progression, and silibinin efficacy to target this response. We collected conditioned media from CAFs treated with vehicle or silibinin, and labeled as control conditioned media (CCM) or silibinin-treatment conditioned media (SBCM), respectively. Next, we characterized the effect of CCM and SBCM treatment in several PCA cell lines (RWPE-1, WPE-1 NA-22, WPE-1 NB-14 and PC3). Result showed that compared with SBCM, CCM significantly reduces E-cadherin expression and increases invasiveness and clonogenicity in PCA cells. Further molecular studies identified monocyte chemotactic protein-1 (MCP-1) as the key component of CCM that promotes PCA invasiveness, whereas silibinin treatment strongly reduced MCP-1 expression in CAFs by inhibiting the DNA-binding activity of MCP-1 transcriptional regulators-nuclear factor-kappaB and AP-1. In vivo, silibinin feeding (200mg/kg body weight) strongly reduced TRAMPC1 allografts growth (by 68%) in syngeneic C57Bl/6 mice. TRAMPC1 tumor analysis showed that silibinin reduced MCP-1 and CAFs' biomarkers (fibroblast activation protein, α-smooth muscle actin, transforming growth factor beta 2, vimentin etc.) and significantly modulated the recruitment of immune cells in the tumor microenvironment. Similar inhibitory effects of silibinin on MCP-1 and immune cells recruitment were also observed in TRAMP PCA tissues with reported silibinin efficacy. Overall, our data suggest that silibinin can target CAF-mediated invasiveness in PCA by inhibiting MCP-1 secretion. This, in turn, was associated with a reduction in immune cell recruitment in vivo along with a marked reduction in tumor growth.
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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.