“Move over, Resveratrol!”: Procyanidins (B2G2) in Grape Seed Extract May Protect Against Prostate Cancer

Prostate cancer is one of the leading causes of death for men in the United States, with cancer in general ranking #2 on this scale.  According to 2012 statistics, about 241,740 new cases of prostate cancer would occur, and about 28,170 Americans would die of prostate cancer-related maladies.   Prostate cancer isn’t exactly a quickly moving disease—in fact, the progression of prostate cancer on average is relatively slow, thus ample opportunities to try and treat or eliminate the disease from the body if caught early enough.  Depending upon the severity of the disease, treatment for prostate cancer can range anywhere from a more “sit and wait” approach, to a more aggressive surgery and radiation therapy approach.  Prostate cancer

Photo by Flickr user Slawekol

Photo by Flickr user Slawekol

treatment research is an ongoing field which is continually attempting to find new treatments with high efficacy and lower risk than some of the more common treatments on the market.

In very simple terms, cancer basically happens when the cells in your body multiply out of control, resulting in the formation of tumors.  If untreated, the body’s cells will continue to proliferate and multiply, eventually causing problems with the major systems that keep you alive and ultimately, death.  Surgical treatments aim to simply remove the tumor, however, if the cancer is more advanced, there is a good chance the cancerous cells have spread to other parts of the body, and more tumors will show up eventually.  Chemotherapy and radiation therapy are also used for cancer treatment, as they kill the cancerous cells in the body.  One unfortunately side effect is that this type of therapy also kills the patient’s healthy cells, which is never a good thing.

Under normal conditions, the body has mechanisms and systems in check for cell cycle development, proliferation/multiplication, and cell death.  When one (or more) of these stages gets “messed up”, you can end up with uncontrolled cellular division and/or multiplication and ultimately cancer.  One player in particular, the gene known as “survivin” (fitting, no?), is responsible for the regulation of cell proliferation and viability in cancerous tumors in humans.  Survivin also inhibits apoptosis of the cells, which in simple terms means that it stops cell death from occurring; thereby the cancerous cells can keep multiplying out of control without any way to kill off the extras and avoid tumor growth.  Mutations in the survivin gene is one of the reasons why chemotherapy treatments are at times ineffective.  Survivin basically keeps the cells alive (i.e. they help them survive) and allows them to continue to multiply and proliferate out of control, despite the presence of any chemotherapy agents.

The polyphenols in red wine have been the focus for anticancer treatments as well as treatments for cardiovascular issues, and treatments for many other types of cancer in humans.  Rather than drink cases upon cases of red wine, which would need to occur if one were to extract the appropriate levels of polyphenols from the beverage and which would ultimately cause even more significant problems for the consumer due to the sheer amount of alcohol consumed, researchers have focused on isolating key compounds from the skins and seeds of the grapes themselves that are known to have significant health benefits, and to market those in a more concentrations treatment form.

Photo by Flickr user zeeweez

Photo by Flickr user zeeweez

Resveratrol is a polyphenol found in red wine, grapes, and skins/seeds, and is historically the most frequently studied compound for use as a dietary health supplement for a variety of maladies.  However, it’s not all about resveratrol, and many of the other polyphenols in grape skins and seeds (as well as the finished wine) that also possess health benefits when consumed.  Specifically, B2 3,3”-di-O-gallate (B2G2), a procyanidin that is found in grape skins and seeds, has been shown be a powerful antioxidant which can function to benefit a wide range of human health problems.  Recently, preliminary data has suggested that B2G2 may stop the progression of prostate cancer in a human cell line, with the follow-up study to be presented to you today.

The overall goal of the study presented today, which was published recently in the journal Nutrition and Cancer, was to determine if B2G2 isolated from grape skins and seeds could be an effective treatment for prostate cancer, focusing on interactions with survivin and other genes known to be connected with prostate cancer proliferation, and if synthetically produced B2G2 would work just as effectively as the naturally extracted procyanadin, since the time and cost of isolating B2G2 directly from grape skins and seeds is long and expensive, while synthetically producing the compound would be a lot less expensive, less time consuming, and would result in significantly greater yields.

Due to the highly technical nature of this study, I won’t go into all the specific details about the methods or the super detailed results, though if you have specific questions about these things, please feel free to leave a comment and ask!

“Test Subjects”

Since this research is still in very early stages, this study used a prostate cancer human cell line for their analysis.  In other words, they used human cells that had been isolated from prostate cancer tumors that would eventually develop into prostate cancer if grown under the appropriate laboratory conditions.  This almost always the natural progression of this type of research, so while the results may not tell us exactly how the treatment will function in an actual human, it will give us a huge clue and could reflect how the treatment would behave in the human body.

Natural B2G2 isolate from grape skin extract compared with synthetically created B2B2

In terms of isolation from grape skins and seeds extract, B2G2 yield was only 0.3% of the total extract, thus confirming that using B2G2 isolate only from natural extracts would be very expensive and time consuming in order to collect the amount necessary for effective treatment levels.  When comparing natural B2G2 isolate with synthetically created B2G2 isolates, the researchers in this study found that the results were near identical, thus allowing the use of synthetically created B2G2 in substitution of naturally isolated B2G2, thereby significantly reducing costs.

B2G2 as a treatment for Prostate Cancer

The results of this study showed that regardless of using natural B2G2 or synthetically created B2G2, B2B2 effectively reduced cell growth and proliferation by inducing cell cycle arrest (i.e. stopping the cell growth process) and also inducing cell death in human prostate cancer cells.  Specifically, B2G2 was shown in this study to inhibit activity of NF-кB and AP1.  Previous studies have shown that down-regulation or inhibition of the expression of these proteins cause both inhibition of cell growth and increased apoptosis and cell death in cancer cell lines, which was confirmed in this study.  Based on these results, the researchers stipulated

Photo by Flickr user Victor Bezrukov: http://www.flickr.com/photos/s-t-r-a-n-g-e/

Photo by Flickr user Victor Bezrukov: http://www.flickr.com/photos/s-t-r-a-n-g-e/

that B2G2 may be “contributing (directly or indirectly) to the apoptosis induction or to anti-inflammatory effect in [human prostate cancer] cells”.  In other words, these results may suggest that B2G2 may induce cell death in human prostate cancer cells, thus behaving as possible effective treatment for prostate cancer in humans.

Another important result of this study was that B2B2 inhibited survivin expression in human prostate cancer cells, which further supports the finding that B2G2 may act as a protector against prostate cancer by reducing cell proliferation and increasing cell death in human prostate cancer cells.  If you recall from earlier, increased expression of survivin results in the inhibition of cell death in cancer cells: thus greater levels of survivin = increased tumor growth.  This study showed that B2G2 decreased survivin levels in a human prostate cancer cell line by inhibiting survivin expression, thus indicating that B2G2 could very well prevent prostate cancer tumor cell growth in human.

Concluding Thoughts

The results of this study are encouraging, in that it appears that B2G2, a procyanadin isolated from grape skins and seeds (and also synthetically created in the lab) protects against prostate cancer growth by inducing cell death and proliferation in a human prostate cancer cell line.  Previous studies in the mouse model concluded similar protective findings, so to see it reproduced in a human cell line is very encouraging.  I would be interested to see if using B2G2 to as a treatment either alone or in combination with current treatments would be effective in clinical trials.  Also, I’d be curious to know if a B2G2 supplement could protect against prostate cancer before it even had a chance to develop.  Finally, could B2G2 be an effective treatment for other cancers?  Or is this a prostate cancer-specific treatment?

I would definitely not go so far as to say drinking red wine helps protect against prostate cancer, as you’d have to drink a significant amount of wine in order to consume the appropriate levels of B2G2 needed to be an effective treatment, however, the isolation of this compound from grape skins or synthetic production of this compound as a possible treatment or possible preventative for prostate cancer is encouraging.

What do you all think of this study?  Please feel free to leave your comments or questions!

Source: Tyagi, A., Raina, K., Shrestha, S.P., Miller, B., Thompson, J.A., Wempe, M.F., Agarwal, R., and Agarwal, C. 2013. Procyanidin B2 3,3”-di-O-gallate, a biologically active constituent of grape seed extract, induces apoptosis in human prostate cancer cells via targeting NF-кB, Stat3, and AP1 transcription factors. Nutrition and Cancer. DOI: 10.1080/01635581.2013.783602

1 comment for ““Move over, Resveratrol!”: Procyanidins (B2G2) in Grape Seed Extract May Protect Against Prostate Cancer

  1. Mike Saunders
    February 13, 2014 at 1:15 pm

    I too am encouraged by this study. And I would like to participate in any sort of current or upcoming study.

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