Milk thistle finally being looked at

[Tom]

I am incouraged that more and more of these "natural" compounds are being prepared for clinical trials. It seems that even the hardcore allopaths are sitting up and taking notice. Keep on screaming to your oncs about what we read and try for our loved ones.

http://www.oncolink.com/resources/article.cfm?c=3&s=8&ss=23&Year=2006&Month=06&id=13271

Milk thistle compound inhibits experimental lung cancer growth
Martha Kerr
Reuters Health
Posting Date: June 27, 2006



Last Updated: 2006-06-27 15:46:38 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Silibinin, a flavanone derived from milk thistle (Silybum marianum) shows anti-tumor activity in lung cancer in mice, investigators at the University of Colorado, Denver, report in the June 21st issue of the Journal of the National Cancer Institute.

Lead investigator Dr. Rana P. Singh told Reuters Health, "We have been studying milk thistle components, silymarin and silibinin, to examine their efficacy and mechanisms against different epithelial cancers for over a decade. Recently, we reported that oral silibinin inhibits human lung carcinoma A549 tumor xenograft growth in athymic nude mice...and forms a novel chemo-combination with doxorubicin."

Dr. Singh's team injected nude mice with urethane, a carcinogen, to induce lung cancer. The animals then received diets containing different doses of silibinin, ranging from 0% to 1%.

"We obtained pure silibinin from Sigma Chemical Co., and silibinin diets were commercially prepared at room temperature and air dried. We did not use milk thistle dietary supplements which are available for human consumption," Dr. Singh said.

Mice fed 1% silibinin had fewer large lung tumors than control mice -- 2 tumors per animal versus 27 tumors/mouse in controls.

The researchers conducted immunohistochemistry and Western blot analysis to determine the presence of angiogenesis and enzyme activity indicating apoptosis, inflammation and proliferation.

They found that silibinin-fed mice had fewer tumors staining positive for cell proliferation markers than control animals. Also, tumor microvessel density was reduced 89% with silibinin (6 microvessels versus 56 microvessels in a 400x field).

Vascular endothelial growth factor expression was inhibited by the milk thistle compound. Also inhibited were inducible nitric oxide and cyclooxygenase-2 enzyme activity, both of which increase VEGF expression.

Dr. Singh added, "We are still pursuing studies of biomarkers, and the mechanisms and therapeutic effect of silibinin in animal models of lung cancer. We expect soon after that clinical trials with silibinin in lung cancer patients will be planned."

Phase I/II trials of silibinin are already underway for the treatment of prostate cancer.

J Natl Cancer Inst 2006;98:846-855.

[al from Canada]

Lung cancer aside, this supplement would be of benefit for any liver mets. al

[heblaj01]

Many in vitro & animal tests have attributed beneficial effects to milk thistle especially for various hepatic diseases. And two of its purified constituants,
silymarin and silibinin (the latter a major component of the former), have also been studied in particular for cancer.

However, the study shown below throws a cautionary warning about silymarin & by extension about milk thistle supplementation.

It should be noted that in the abstract on the silibin beneficial effect on lung cancer in mice the researchers specifically mentioned they did not use milk thisle but purified silibinin.
If these studies apply to humans, it would mean that milk thistle is a complex chemical with opposite properties as far as cancer is concerned.
It does point to the importance of purified chemicals in medical experiments to show non anbiguous results.
Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary supplements.

Malewicz B (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Malewicz+B%22%5BAuthor%5D), Wang Z (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Wang+Z%22%5BAuthor%5D), Jiang C (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Jiang+C%22%5BAuthor%5D), Guo J (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Guo+J%22%5BAuthor%5D), Cleary MP (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Cleary+MP%22%5BAuthor%5D), Grande JP (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Grande+JP%22%5BAuthor%5D), Lu J (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Lu+J%22%5BAuthor%5D).

The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912.

Silymarin is a mixture of polyphenolic flavonoids isolated from milk thistle (Silybum marianum) with anti-cancer activities reported in 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-mammary tumors 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.

[Tom]

Thanks Hebla,

I should always ad the caveat when posting, that Mom's tumors were ER-, as that makes a tremendous diffeence when considering diet/vitamin options for treatment. Milk thistle's benefits for hepatic concerns are what usually prompt people to use it. All considerations for herbal/natural treatments should be thoroughly researched, as some of these things have unusual side effects when used in the presence of various types of malignancies. Thanks agin for the post.

Tom

[heblaj01]

This article on silibinin (also spelled silibin,silybin,silybinin) the major part of silymarin in milk thistle shows activity against Hepatocellular Carcinoma in laboratory cell experiments:

http://clincancerres.aacrjournals.org/cgi/content/abstract/11/23/8441 (http://clincancerres.aacrjournals.org/cgi/content/abstract/11/23/8441)
Silibinin Efficacy against Human Hepatocellular Carcinoma

This adds an other hint of efficacy of milk thistle extracts againts cancer to the one shown in the first post (by Tom) of this thread on lung cancer

[StephN]

I have mentioned more than once on this board that I took Milk Thistle daily while taking Taxol, Navelbine and Herceptin for extensive ("too numerous to count") liver mets. The chemos lasted for 27 weekly treatments to reach NED. I kept on with the Milk thistle for another 5 or 6 months. Now I hardly ever take it as I take some other supplements. Maybe I want to keep taking it??

Like Tom's Mom, I am ER and PR negative. So always looking for what else I can do to boost my immune system and stay NED after being stage IV for almost 5 years now (can hardly believe I am saying that - 5 years!!).

[sarah]

Congrats Steph on the 5 year mark!
sarah

[heblaj01]

In this article Milk Thisle is shown not to inhibit Human Cytochrome P450 3A.
I am not knowledgeable in biochemistry:
does it follow that Milk Thisle (& its components Silymarin & Silybinin) is not likely to interfere with chemo drugs which use Cytochrome P450 3A for their metabolism?
Any opinion?

http://jcp.sagepub.com/cgi/content/abstract/46/2/201
Assessing the Clinical Significance of Botanical Supplementation on Human Cytochrome P450 3A Activity: Comparison of a Milk Thistle and Black Cohosh Product to Rifampin and Clarithromycin

P.S.
I have read that Silybinin is the main if not the only active ingredient in Milk Thisle for liver supplementation & furthermore that the Silybinin Phytosome version is better for bioavailability.
Anyone agrees or disagrees?

[Joy]

Hey guys, I've taken milk thistle over the years as I've battled BC. The info posted here causes me to ask for some opinions. My cancer is ER+/PR+ (her2+++) and my real area of concern is the liver. Up until the last year I've had good contorl over it with various hormonal and chemo treatments. I also think that my supplements/acupuncture, etc. has mad a difference. Should I even be taking the milk thistle? Also as far as liver cleansing stuff, i was thinking that it is best to take those up until a day before tx and after the drug's half life. My only thinking being that the whole point of chemo is to get in my liver and be toxic to the tumors, so I might as well let that happen, then support the poor thing until the next time. Is that dumb? I'm on Navlebine and herceptin weekly (navelbine has a half life of approximately 46 hours).

Thanks for any feedback!

And WAY TO GO STEPH! You are a hero, how is the noggin?

[heblaj01]

The more I search & the more I find interesting bits of info on Silybinin.
In the long article below which appears well researched on various conventional & alternative treatments for brain cancer I extracted this section:

"Silibinin (an ingredient of Silymarin)
http://www.virtualtrials.com/images/space.gif Silymarin is an extract from the milk thistle plant that has been used extensively in Europe as an antidote for liver toxicity, due to mushroom poisoning and overdoses of tylenol. Its active ingredient is a molecule called silibinin. Recently a great deal of laboratory research has shown it to have anti-cancer effects as well. Like genistein and quercetin it is a tyrosine kinase inhibitor, but it appears to have multiple other effects, including the inhibition of the insulin-like growth factor (IGF) that contributes to the development of chemoresistance (141) (see the section on tamoxifen), and the inhibition of angiogenesis (142). It also inhibits the 5-lipoxygenase inflammatory pathway and suppresses nuclear factor kappa B, which is known to be antagonistic to apoptosis (143) It also appears to protect against common chemotherapy toxicities (144), while at the same time increasing the effectiveness of chemotherapy (145)."

http://www.virtualtrials.com/printwilliams.cfm (http://www.virtualtrials.com/printwilliams.cfm)
Treatment Options for Glioblastoma and other Gliomas

Prepared by Ben A. Williams



Glioblastoma Diagnosis, March, 1995 Last Updated: September 9, 2004

[heblaj01]

In previous posts in this thread Tom & myself highlighted the lab experiments which showed beneficial activity of Silybin (an extract of Silymarin, the main ingredient in Milk Thistle) against various cancer cell lines (primary lung, liver,brain).
In follow up search for more info on the subject I discovered a few disquieting bits of data regarding two negative aspects of Silybin (& its related parent compounds).
None of the info I read is definitive since no human study has been done to confirm the lab findings & my limited understanding of the data may be flawed, but caution is of the order.

The first bit is the inhibition of P450 3A4 (ref 1 below) which is necessary for the proper metabolism of some chemo drugs such as Vinorelbine(Navelbine).
However since inhibition of P450 3A4 is in some cases limited to the guts (& does not always extend to the liver) Silybin & the chemo drug would have to be both taken by mouth. So in the case of Vinorelbine which taken by I.V. the risk of interaction is perhaps nil. (There is a pill version of Vinorelbine which would appear to be more problematic if taken with Silybin).
In addition Silybin inhibits UGT1A1 which has been associated with protection against some cancers (Ref.2) & is necessary for the metabolism of the drug Irinotecan(would increase its toxicity by lengthening its stay in the body).

The second bit of negative info is related to the potential effect on ER+ cancer cells. In all of the papers I have read so far about the beneficial activity of Silybin no estrogen positive cells were tested. The beneficial effects were demonstrated on primary cancer cells in lung, liver etc...not on metastatic cells from breast in these organs.
I found two papers demonstrating adverse effects of Silymarin on the proliferation of ER+ cells (Ref.3 & 4).
Since experiments showing anticancer activity used pure Silybin while those showing adverse effects were using the parent Silymarin there was still the possibility that adverse effects were caused by chemicals in Silymarin other than Silybin. Trying to find an answer to that question on internet proved fruitless & I had to querry by E-mail one of the researchers involved in the Silybin studies. His reply was that he knew of no study on this matter but that he assumed that the negative effects on ER+ cells caused by Silymarin would be the same for pure Silybin (& consequently for milk thistle as well).

If all of these findings & speculations are applicable to women with ER+ or at risk of ER+ cancer then taking Milk Thistle or Silymarin or Silybin is potentially increasing the risk of proliferation.

It is quite disappointing that these supplements may be double edge swords perhaps helpfull against some cancers & appearing adverse for others.


Ref.1
http://dmd.aspetjournals.org/cgi/content/full/32/6/587 (http://dmd.aspetjournals.org/cgi/content/full/32/6/587)
SILYBIN INACTIVATES CYTOCHROMES P450 3A4 AND 2C9 AND INHIBITS MAJOR HEPATIC GLUCURONOSYLTRANSFERASES
Ref.2
http://breast-cancer-research.com/content/7/6/r909 (http://breast-cancer-research.com/content/7/6/r909)
Genetic polymorphisms in human SULT1A1 and UGT1A1 genes associate with breast tumor characteristics: a case-series study.
Ref.3
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=14568570&query_hl=23&itool=pubmed_docsum (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=14568570&query_hl=23&itool=pubmed_docsum)
Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx) rats.
Ref.4
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16597642&query_hl=26&itool=pubmed_docsum (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16597642&query_hl=26&itool=pubmed_docsum)
Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary supplements.