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Silibinin (ULTRA SYLIMARIN)

Silibinin, the most prominent of these compounds, accounts for about 60% of the weight of silymarin, and is believed to be responsible for most of the liver-protective activity of silymarin and milk thistle extract.  Just within the last decade, scientists have learned that silibinin has considerable potential for preventing and treating cancer.

In concentrations that may be feasible to achieve with high-dose clinical regimens, silibinin has been shown to have growth inhibitory effects on a wide range of human cancer cell lines including cancers arising from the prostate, breast, colon, lung, liver, bladder and cervix.  Silibinin can suppress the proliferation of these cells, while at the same time increasing the rate at which they die by apoptosis.  In addition, silibinin can sensitize cancer cell lines to the killing effects of certain cytotoxic chemotherapeutic drugs.  Thus, silibinin may have potential both for retarding the growth and spread of cancer and for boosting the response of cancers to chemotherapy.

The mechanisms responsible for these effects have been studied most intensively in human prostate cancer cells. It should first be noted that these studies show that concentrations of silibinin, which retard the growth of these prostate cancers, do not influence the growth of healthy normal prostate cells. In other words, the effects of silibinin on cell proliferation appear to be specific to cancer cells. The anti-proliferative effects of silibinin on prostate cancer cells have been traced to decreased function of the epidermal growth factor receptor (EGF-R).  This is a key mediator of growth signals in prostate cancer and in many other types of cancer.  Silibinin binds to this receptor and prevents it from interacting with hormones that activate it – some of which are produced by prostate cancers.  Furthermore, silibinin induces prostate cancer cells to make more of a compound, known as IGFBP-3, that binds to and inhibits the activity of insulin-like growth factor-I (IGF-I), a key growth factor for many cancers.   IGF-I is produced by the liver and circulates in the blood, where it acts to promote tissue growth throughout the body.  In addition, some cancers can make their own IGF-I.

As if these benefits weren’t enough, silibinin has also been shown to suppress the NF-kappaB signaling pathway.  The effect of silibinin on NF-kappaB helps to rationalize silibinin’s ability to increase the sensitivity of cancers to certain chemotherapy drugs.  The effects of silibinin on EGF-R, which likewise promotes cancer cell survival, also contribute in this regard. 

The impact of orally administered silibinin on the growth of human tumors in immunodeficient mice has been studied with three different types of tumors – prostate, lung and ovarian.  In each case, silibinin has been found to have a substantial and dose-dependent suppressive effect on tumor growth in doses that had no apparent toxicity to the treated animals. 

Examination of the silibinin-treated tumors revealed that they had a much less developed vasculature than control tumors.  In other words, there were less blood vessels in the tumor to provide nourishment and oxygen.  Follow-up studies showed that in some cancers silibinin could suppress secretion of the  pro-angiogenic factor VEGF.  Furthermore, other studies show that clinically feasible concentrations of silibinin have a direct effect on endothelial cells.  Silibinin can suppress the proliferation of these cells and reduce their ability to migrate, invade tissues and roll themselves into tubes, which is how new blood vessels are formed.  These findings suggest that the growth-slowing impact of silibinin on tumors reflects the interaction of at least three phenomena: a direct anti-proliferative effect on cancer cells; a suppression of VEGF production by these cells; and a direct inhibitory effect on the capacity of endothelial cells to build new blood vessels.  Silibinin deserves a gold medal!

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The I pray to you, O Lord. I say, "You are my place of refuge. You are all I really want in life." Psalm 142:5

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