ArticleMolecular carcinogenesis2014
Silibinin inhibits prostate cancer cells- and RANKL-induced osteoclastogenesis by targeting NFATc1, NF-κB, and AP-1 activation in RAW264.7 cells.
Article in Molecular carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Phytochemicals in Inhibition of Prostate Cancer: Evidence from Molecular Mechanisms Studies.Biomolecules · 2022Pooled it
- Melittin acupoint injection in attenuating bone erosion in collagen-induced arthritis mice via inhibition of the RANKL/NF-κB signaling pathway.Quantitative imaging in medicine and surgery · 2023Article
- Role of Plant-Derived Compounds in the Molecular Pathways Related to Inflammation.International journal of molecular sciences · 2023Review
- KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK.Nutrients · 2022Article
- Therapeutic Effects of Silibinin Against Polycystic Ovary Syndrome Induced by Letrozole in Rats via Its Potential Anti-Inflammatory and Anti-Oxidant Activities.Journal of inflammation research · 2022Article
- Genkwanin Prevents Lipopolysaccharide-Induced Inflammatory Bone Destruction and Ovariectomy-Induced Bone Loss.Frontiers in nutrition · 2022Article
- Chemical Profile, Antioxidant, Anti-Inflammatory, and Anti-Cancer Effects of ItalianAntioxidants (Basel, Switzerland) · 2020Article
- Canine prostatic cancer cell line (LuMa) with osteoblastic bone metastasis.The Prostate · 2020Article
- Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion.Cell communication and signaling : CCS · 2019Article
- Review
- Calcium and Nuclear Signaling in Prostate Cancer.International journal of molecular sciences · 2018Review
- Silibinin alleviates inflammation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes and has a therapeutic effect on arthritis in rats.Scientific reports · 2018Article
- Molecular signaling mechanisms behind polyphenol-induced bone anabolism.Phytochemistry reviews : proceedings of the Phytochemical Society of Europe · 2017Review
- Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.Cancer prevention research (Philadelphia, Pa.) · 2016Article
- Article
- Beneficial effects of the naturally occurring flavonoid silibinin on the prostate cancer microenvironment: role of monocyte chemotactic protein-1 and immune cell recruitment.Carcinogenesis · 2016Article
- Potential Effects of Silymarin and Its Flavonolignan Components in Patients with β-Thalassemia Major: A Comprehensive Review in 2015.Advances in pharmacological sciences · 2016Review
- Silibinin and its 2,3-dehydro-derivative inhibit basal cell carcinoma growth via suppression of mitogenic signaling and transcription factors activation.Molecular carcinogenesis · 2016Article
- Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin.Toxicology and applied pharmacology · 2015Article
- [Prostate cancer prophylaxis by dietary supplements: more than just an illusion?].Der Urologe. Ausg. A · 2014Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Currently, there are limited therapeutic options against bone metastatic prostate cancer (PCA), which is primarily responsible for high mortality and morbidity in PCA patients. Enhanced osteoclastogenesis is an essential feature associated with metastatic PCA in the bone microenvironment. Silibinin, an effective chemopreventive agent, is in phase II clinical trials in PCA patients but its efficacy against PCA cells-induced osteoclastogenesis is largely unknown. Accordingly, here we examined silibinin effect on PCA cells-induced osteoclastogenesis employing human PCA (PC3MM2, PC3, and C4-2B) and murine macrophage RAW264.7 cells. We also assessed silibinin effect on receptor activator of nuclear factor κB ligand (RANKL)-induced signaling associated with osteoclast differentiation in RAW264.7 cells. Further, we analyzed silibinin effect on osteomimicry biomarkers in PCA cells. Results revealed that silibinin (30-90 μM) inhibits PCA cells-induced osteoclast activity and differentiation in RAW264.7 cells via modulating expression of several cytokines (IGF-1, TGF-β, TNF-α, I-TAC, M-CSF, G-CSF, GM-CSF, etc.) that are important in osteoclastogenesis. Additionally, in RAW264.7 cells, silibinin decreased the RANKL-induced expression and nuclear localization of NFATc1, which is considered the master regulator of osteoclastogenesis. Furthermore, silibinin decreased the RANKL-induced DNA binding activity of NFATc1 and its regulators NF-κB and AP1, and the protein expression of osteoclast specific markers (TRAP, OSCAR, and cathepsin K). Importantly, silibinin also decreased the expression of osteomimicry biomarkers (RANKL, Runx2, osteocalcin, and PTHrP) in cell culture (PC3 and C4-2B cells) and/or in PC3 tumors. Together, our findings showing that silibinin inhibits PCA cells-induced osteoclastogenesis, suggest that silibinin could be useful clinically against bone metastatic PCA.
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Registered trials
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