Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary supplements.
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Cleary, Margot P.
Grande, Joseph P.
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AbstractSilymarin is a mixture of polyphenolic flavonoids isolated from milk thistle (Silybum marianum) with anticancer activities reported for several organ sites. The present study tested the efficacy of dietary silymarin against mammary carcinogenesis in two rodent models. In the Sprague-Dawley rat model, female rats were fed a purified diet supplemented with none, 0.03, 0.1, 0.3 or 1% (w/w) of silymarin from 21 days of age (DOA) and carcinogenesis was initiated by a single i.p. injection of 1-methyl-1-nitrosourea (MNU) at 51 DOA. Mammary tumor (MT) development was followed till 110 days after carcinogen injection. In the MMTV-neu/HER2 transgenic mouse mammary carcinogenesis model, homozygous transgenic females were fed a purified diet supplemented with none or 0.3% silymarin, either from 28 or 120 DOA and MT development was followed to approximately 300 DOA. The results showed that dietary silymarin increased the plasma concentration of free and total silibinin, a major component of silymarin, in a dose-dependent manner in the rat, but did not decrease either MT incidence or number. Instead silymarin modestly increased the number of MNU-induced MTs in rats. Similarly, silymarin increased MT incidence and multiplicity and non-MTs in the neu-transgenic mice. In cell culture, treatment of human MCF-7 breast cancer cells with serum-achievable concentrations of silymarin in the rodent models stimulated their growth, in part through an estrogen-like activity. Because silymarin is being used in the treatment of liver cirrhosis and a variety of other human ailments, and is sold as a dietary supplement, our findings add a cautionary note to its application in breast cancer prevention.
CitationCarcinogenesis 2006, 27 (9):1739-1747
DescriptionDietary modulation of carcinogenesis-related pathwaysDietary item or component studied: silymarinPathways studied: inhibition of mitogenic signaling molecules, induction of kip1/p27, cellular G1 arrest cell growth inhibition and apoptosisStudy type (in vitro, animals, humans): Sprague-Dawley rats and MMTV-new/Her2 transgenic miceTissue/biological material/sample size: 300μl plasma samplesMode of exposure (if in vivo) (acute, chronic, root of exposure): diet and i.p. InjectionImpact on pathway (including dose-response): Sprague-Dawley rats: 30-40% tumors increase, MMTV-new/Her2: 30-35% tumors increase, x2=3.32, 0.0 <p<0.1 Keywords classification: Animals;biomarkers of dietary exposure;Cell Line,Tumor;Diet;dietary modulation of cancer & cancer biomarkers;Dietary Supplements;Female;Mammary Neoplasms,Experimental;metabolism;Mice;Mice,Transgenic;Milk Thistle;Minnesota;pathology;pharmacology;prevention & control;Rats;Rats,Sprague-Dawley;Research;Silymarin;validation;humans;analysis;
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