ArticleBMC cancer2013
Chemoprevention utility of silibinin and Cdk4 pathway inhibition in Apc(-/+) mice.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
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- Therapeutic effects of natural polyphenols on colorectal adenomas: Focus on preclinical studies (Review).Oncology reports · 2023Review
- Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Review
- Cyclin-Dependent Kinase Inhibitors and Their Therapeutic Potential in Colorectal Cancer Treatment.Frontiers in pharmacology · 2021Review
- Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity.Molecules (Basel, Switzerland) · 2020Review
- Silibinin and colorectal cancer chemoprevention: a comprehensive review on mechanisms and efficacy.Journal of biomedical research · 2016Review
- Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression.Oncotarget · 2016Article
- Differential control of growth, apoptotic activity and gene expression in human colon cancer cells by extracts derived from medicinal herbs, Rhazya stricta and Zingiber officinale and their combination.World journal of gastroenterology · 2014Article
- Knocking down CDK4 mediates the elevation of let-7c suppressing cell growth in nasopharyngeal carcinoma.BMC cancer · 2014Article
- Prom1 function in development, intestinal inflammation, and intestinal tumorigenesis.Frontiers in oncology · 2014Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundColorectal cancer (CRC) is the second leading cause of death from cancer in the United States. Colorectal cancers have a prolonged latency following initiation that may span decades providing ample time for implementing a chemoprevention strategy that could block or reverse the progression to CRC. Cdk4 pathway alterations have been linked to a number of cancers including CRC. In these experiments we focused on the Cdk4 pathway and its role in intestinal tumorigenesis as a possible target in chemoprevention strategies.
methodsWe evaluated the effect of Cdk4 blockade on the prevention of intestinal tumor formation by crossing Cdk4(-/-) mice to Apc(-/+) mice. In addition, we tested the effect of the dietary compound silibinin on the Cdk4 pathway in Apc(-/+) mice and HT-29 colon cancer cells in culture.
resultsCdk4(-/-) mice backcrossed to Apc(-/+) mice reduced intestinal adenoma formation compared to Apc(-/+) controls. Silibinin effectively targeted the Cdk4 pathway causing hypophosphorylation of the retinoblastoma protein, inhibited cell growth, and induced apoptosis. As a result silibinin blocked the development of intestinal adenomas by 52% in this genetic model (Apc(-/+) mice) of early events in colorectal cancer formation. No toxic abnormalities were detected in mice which received silibinin.
conclusionsModification of the Cdk4 pathway using a natural plant-derived compound such as silibinin may be a useful chemopreventive strategy for colorectal carcinomas.
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