ArticleMolecular carcinogenesis2015
Silibinin prevents prostate cancer cell-mediated differentiation of naïve fibroblasts into cancer-associated fibroblast phenotype by targeting TGF β2.
Article in Molecular carcinogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
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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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The Radiosensitizing Potentials of Silymarin/Silibinin in Cancer: A Systematic Review.Current medicinal chemistry · 2024Pooled it
- Emerging agents that target signaling pathways in cancer fibroblast cells (Review).International journal of oncology · 2026Review
- 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
- Prostate Cancer-Associated Fibroblasts: A Review on CAF Functions, Heterogeneity, Resistance Mechanisms, and Future in a Chip.International journal of molecular sciences · 2026Review
- The Role of Distinct Cancer-Associated Fibroblast Subtypes in Prostate Cancer Immunotherapy.International journal of biological sciences · 2026Review
- Review
- Molecular Evidence of the Bio-activities of Traditional Home Medicine Ingredients.Current topics in medicinal chemistry · 2025Review
- Synergistic effect of the sphingosine kinase inhibitor safingol in combination with 2'-nitroflavone in breast cancer.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Genomic analyses of intricate interaction of TE-lncRNA overlapping genes with miRNAs in human diseases.Genes & genomics · 2024Article
- The axis of tumor-associated macrophages, extracellular matrix proteins, and cancer-associated fibroblasts in oncogenesis.Cancer cell international · 2024Review
- Cancer-associated fibroblasts and prostate cancer stem cells: crosstalk mechanisms and implications for disease progression.Frontiers in cell and developmental biology · 2024Review
- Cancer-associated fibroblasts promote malignant phenotypes of prostate cancer cells via autophagy : Cancer-associated fibroblasts promote prostate cancer development.Apoptosis : an international journal on programmed cell death · 2023Article
- Immunotherapy for lung cancer combining the oligodeoxynucleotides of TLR9 agonist and TGF-β2 inhibitor.Cancer immunology, immunotherapy : CII · 2023Article
- Targeting extracellular matrix through phytochemicals: a promising approach of multi-step actions on the treatment and prevention of cancer.Frontiers in pharmacology · 2023Review
- Anti-prostate cancer protection and therapy in the framework of predictive, preventive and personalised medicine - comprehensive effects of phytochemicals in primary, secondary and tertiary care.The EPMA journal · 2022Review
- From Therapy Resistance to Targeted Therapies in Prostate Cancer.Frontiers in oncology · 2022Review
- Flavonoids against non-physiologic inflammation attributed to cancer initiation, development, and progression-3PM pathways.The EPMA journal · 2021Review
- Natural products remodel cancer-associated fibroblasts in desmoplastic tumors.Acta pharmaceutica Sinica. B · 2020Review
- Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science.Cancer medicine · 2019Review
- Profiling Prostate Cancer Therapeutic Resistance.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Tumor microenvironment (TM) is an essential element in prostate cancer (PCA), offering unique opportunities for its prevention. TM includes naïve fibroblasts that are recruited by nascent neoplastic lesion and altered into 'cancer-associated fibroblasts' (CAFs) that promote PCA. A better understanding and targeting of interaction between PCA cells and fibroblasts and inhibiting CAF phenotype through non-toxic agents are novel approaches to prevent PCA progression. One well-studied cancer chemopreventive agent is silibinin, and thus, we examined its efficacy against PCA cells-mediated differentiation of naïve fibroblasts into a myofibroblastic-phenotype similar to that found in CAFs. Silibinin's direct inhibitory effect on the phenotype of CAFs derived directly from PCA patients was also assessed. Human prostate stromal cells (PrSCs) exposed to control conditioned media (CCM) from human PCA PC3 cells showed more invasiveness, with increased alpha-smooth muscle actin (α-SMA) and vimentin expression, and differentiation into a phenotype we identified in CAFs. Importantly, silibinin (at physiologically achievable concentrations) inhibited α-SMA expression and invasiveness in differentiated fibroblasts and prostate CAFs directly, as well as indirectly by targeting PCA cells. The observed increase in α-SMA and CAF-like phenotype was transforming growth factor (TGF) β2 dependent, which was strongly inhibited by silibinin. Furthermore, induction of α-SMA and CAF phenotype by CCM were also strongly inhibited by a TGFβ2-neutralizing antibody. The inhibitory effect of silibinin on TGFβ2 expression and CAF-like biomarkers was also observed in PC3 tumors. Together, these findings highlight the potential usefulness of silibinin in PCA prevention through targeting the CAF phenotype in the prostate TM.
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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.