ArticleCancer prevention research (Philadelphia, Pa.)2013
Direct targeting of MEK1/2 and RSK2 by silybin induces cell-cycle arrest and inhibits melanoma cell growth.
Article in Cancer prevention research (Philadelphia, Pa.), 2013. 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 abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Therapeutic effects of silibinin in preclinical animal models of gastrointestinal cancers: a systematic review and meta‑analysis.BMC cancer · 2026Pooled it
- RSK2 and its binding partners: an emerging signaling node in cancers.Archives of pharmacal research · 2025Review
- Nanodelivery Approaches of Phytoactives for Skin Cancers: Current and Future Perspectives.Current pharmaceutical biotechnology · 2025Review
- Targeting RSK2 in Cancer Therapy: A Review of Natural Products.Anti-cancer agents in medicinal chemistry · 2025Review
- Natural products as therapeutics for malignant melanoma: preclinical evidence and mechanism.Frontiers in pharmacology · 2025Review
- Bovine Serum Albumin Nanoparticles Enhanced the Intranasal Bioavailability of Silybin in Rats.Pharmaceutics · 2023Article
- Morin Hydrate Encapsulation and Release from Mesoporous Silica Nanoparticles for Melanoma Therapy.Molecules (Basel, Switzerland) · 2023Article
- Drug Delivery Systems and Flavonoids: Current Knowledge in Melanoma Treatment and Future Perspectives.Micromachines · 2022Review
- Combination of RSK inhibitor LJH-685 and FLT3 inhibitor FF-10101 promoted apoptosis and proliferation inhibition of AML cell lines.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Selected Flavonoids to Target Melanoma: A Perspective in Nanoengineering Delivery Systems.Bioengineering (Basel, Switzerland) · 2022Review
- Chemical Structure, Sources and Role of Bioactive Flavonoids in Cancer Prevention: A Review.Plants (Basel, Switzerland) · 2022Review
- RSK2 promotes melanoma cell proliferation and vemurafenib resistanceFrontiers in pharmacology · 2022Article
- Valuable Hepatoprotective Plants - How Can We Optimize Waste Free Uses of Such Highly Versatile Resources?Frontiers in pharmacology · 2021Review
- Association BetweenFrontiers in genetics · 2021Review
- Alternative Options for Skin Cancer Therapy via Regulation of AKT and Related Signaling Pathways.International journal of molecular sciences · 2020Review
- Developing a high-performance liquid chromatography fast and accurate method for quantification of silibinin.BMC research notes · 2019Article
- Natural Products and Synthetic Analogs as a Source of Antitumor Drugs.Biomolecules · 2019Review
- Effects of Silymarin-Loaded Nanoparticles on HT-29 Human Colon Cancer Cells.Medicina (Kaunas, Lithuania) · 2018Article
- Potential therapeutic targets of epithelial-mesenchymal transition in melanoma.Cancer letters · 2017Review
- Phytochemicals for the Management of Melanoma.Mini reviews in medicinal chemistry · 2016Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Abnormal functioning of multiple gene products underlies the neoplastic transformation of cells. Thus, chemopreventive and/or chemotherapeutic agents with multigene targets hold promise in the development of effective anticancer drugs. Silybin, a component of milk thistle, is a natural anticancer agent. In the present study, we investigated the effect of silybin on melanoma cell growth and elucidated its molecular targets. Our study revealed that silybin attenuated the growth of melanoma xenograft tumors in nude mice. Silybin inhibited the kinase activity of mitogen-activated protein kinase (MEK)-1/2 and ribosomal S6 kinase (RSK)-2 in melanoma cells. The direct binding of silybin with MEK1/2 and RSK2 was explored using a computational docking model. Treatment of melanoma cells with silybin attenuated the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 and RSK2, which are regulated by the upstream kinases MEK1/2. The blockade of MEK1/2-ERK1/2-RSK2 signaling by silybin resulted in a reduced activation of NF-κB, activator protein-1, and STAT3, which are transcriptional regulators of a variety of proliferative genes in melanomas. Silybin, by blocking the activation of these transcription factors, induced cell-cycle arrest at the G1 phase and inhibited melanoma cell growth in vitro and in vivo. Taken together, silybin suppresses melanoma growth by directly targeting MEK- and RSK-mediated signaling pathways.
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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.