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Milk Thistle (PDQ®): Complementary and alternative medicine - Health Professional Information [NCI] - Laboratory / Animal / Preclinical Studies

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A number of laboratory studies have investigated the effect of silymarin or silybin on the efficacy and toxicity of chemotherapy agents or have measured their direct cytotoxic activity. In an investigation of the effect of a variety of flavonoids on the formation of DNA damage, silymarin did not induce DNA damage in colon (Caco-2) cells, hepatoma (HepG2) cells, and human lymphocytes.[12] At higher concentrations of silymarin (400–1,000 μmol/L) DNA damage was induced in an epithelial cell line (HeLa cells). At higher concentrations (1,000 μmol/L) DNA damage was observed in human lymphocytes. Cell growth was inhibited as the flavonoid concentration was increased in human lymphocytes and HeLa cells. Only at very high concentrations was cell viability affected by silymarin in HepG2 cells. Although this study demonstrated that the flavonolignans of Silybum marianum (L.) are capable of inhibiting cellular proliferation and inducing DNA strand breaks, the results were obtained at very high concentrations that may be difficult to achieve in humans. This study also showed that silymarin does not stimulate cell growth in the HeLa, Burkitt lymphoma, and human hepatoma cell lines.

Silymarin has also been investigated as a possible adjunctive agent in mitigating some of the toxicity associated with chemotherapy agents. Silybin and silychristin exerted a protective effect on monkey kidney cells exposed to vincristine and especially cisplatin chemotherapy.[49] Silybin (200 mg/kg body weight) administration with cisplatin in rats resulted in statistically significant reductions in measures of kidney toxicity.[50] Significant decreases in weight loss, faster recovery of urinary osmolality measures, and depressions in the increase in activity of urinary alanine aminopeptidase ([AAP], a marker of kidney toxicity) were observed. Silybin had no effect on magnesium excretion or glomerular function. Silybin (2 g /kg body weight) administration in rats receiving cisplatin prevented reductions in creatinine clearance, increases in urea plasma levels, and large increases in urinary AAP.[51] No effect on magnesium excretion was observed. Silybin did not interfere with the antineoplastic effects of cisplatin or ifosfamide in germ cell tumors. In experiments with ovarian and breast cancer cell lines, silybin potentiated the effect of cisplatin and doxorubicin.[13] IdB 1,016, a form of silybin bound to a phospholipid complex, was found to enhance the activity of cisplatin against A2780 ovarian cancer cells but had no effect on its own.[52] Silybin increased the chemosensitivity of DU 145 prostate cancer cells resistant to chemotherapy.[53]

Studies have also investigated the effect of silymarin on tumor initiation and promotion. Silymarin appears to have a chemopreventive effect through perturbations in the cell cycle, altering cell signaling that induces cellular proliferation, affecting angiogenesis, or through its anti-inflammatory properties.[1,7,13,19,54] These findings have been supported in human prostate, breast, ectocervical, ovarian, hepatic, leukemia, and epidermoid cell lines.[4,7,9,10,15,55] An investigation of the effect of silymarin on ultraviolet B radiation-induced nonmelanoma skin cancer in mice found that silymarin treatment significantly reduced tumor incidence (P < .003), tumor multiplicity (P < .0001), and tumor volume (P < .0001).[19] These findings suggest that silymarin plays a prominent role in the reduction of cancer cells and in preventing the formation of cancer cells. A number of studies have investigated the mechanism through, which silymarin may affect tumor promotion in mouse skin tumor models. Studies have found that silymarin reduces transcription of markers of tumor promotion and activity,[19] inhibits transcription of tumor promoters,[56] stimulates antioxidant activities,[19,23] interferes with cell signaling,[55] inhibits inflammatory actions,[19,22] and modulates cell-cycle regulation.[57]

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WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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