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Grape Seed Extract Halts Cell Cycle, Checking Growth Of Colorectal Tumors In Mice
Science Daily ^ | October 29, 2006 | American Assoiation of Cancer Research

Posted on 11/13/2006 5:32:05 PM PST by ConservativeMind

Chemicals found in grape seeds significantly inhibited growth of colorectal tumors in both cell cultures and in mice, according to researchers who have already demonstrated the extract's anti-cancer effects in other tumor types.

Their study, published in the October 18 issue of Clinical Cancer Research, documented a 44 percent reduction of advanced colorectal tumors in the animals, and also revealed, for the first time, the molecular mechanism by which grape seed extract works to inhibit cancer growth. The authors found that it increases availability of a critical protein, Cip1/p21, in tumors that effectively freezes the cell cycle, and often pushes a cancer cell to self destruct.

"With these results, we are not suggesting that people run out and buy and use grape seed extract. That could be dangerous since so little is known about doses and side effects," said Rajesh Agarwal, Ph.D., professor in the Department of Pharmaceutical Sciences at the University of Colorado Health Sciences Center in Denver.

"The value of this preclinical study is that it shows grape seed extract can attack cancer, and how it works, but much more investigation will be needed before these chemicals can be tested as a human cancer treatment and preventive," he said.

The skin and seeds of grapes are a rich source of proanthocyanidins, a class of antioxidant flavonoids that remove harmful free oxygen radicals from cells. Grape products (juice and red wine) are known for their heart healthy effects, especially in lowering levels of blood cholesterol, Agarwal said, and because grape seeds contain higher concentrations of these chemicals, they are widely marketed as a dietary supplement.

Agarwal and his team of investigators were first to report, in 1999, that grape seed extract also has chemopreventive activity against skin cancer. Their subsequent preclinical work has shown that the extract also retards growth of prostate cancer cells.

In this study, Agarwal tested the extract on colorectal cancer, the second most common malignancy in Americans as well as the second leading cause of cancer deaths in this country. They exposed two different human colon carcinoma cells to the extract, and found a dose- and time-dependent inhibition of cell growth.

"Beneficial effects were correlated with how much extract was used and how long it was used for," Agarwal said. The number of live cells decreased by 92 percent in one cell line when the highest dose was given for the longest time period, which was two days, he said.

The researchers then performed a cell cycle distribution analysis, looking to see specific growth inhibitory effects. They found that the longer the extract was used, the more cells were "arrested" in the G1 phase of the cell cycle, the time when the cell is preparing to duplicates its DNA before dividing, and, correspondingly fewer cells had advanced to the "S" phase, when DNA is being actively duplicated.

They then studied the extract's effect on the molecular regulators that control the cell cycle, and found a strong dose-dependent increase in Cip1/p21 protein. In fact, the amount of Cip1/p21 protein within the cells increased by more than 150 times after 12 hours of treatment, Agarwal said. The researchers also noted a corresponding decrease in a number of different cyclin proteins and associated cyclin-dependent kinases (CDKs).

This all makes sense, according to Agarwal. One of the hallmarks of cancer is rampant cell growth due to loss of control of the cell cycle, and CDKs help push the cycle from a quiet state through to cell division. The Cip1/p21 protein, however, is powerful enough to inhibit the activity of CDKs and can also control apoptosis, or programmed cell death, he said.

"This protein physically interacts with CDKs," Agarwal said. "In normal cells, it attaches to CDKs to inhibit growth, but if a cell wants to grow, as it does in cancer, levels of Cip1/p21 are reduced, or non-functional."

Indeed, further experimentation demonstrated that grape seed extract increased the level of Cip1/p21 protein, allowing it to bind to and shut down the CDKs driving the cell cycle. The investigators also found that the extract can do that even if a cancer cell is missing p53 function (which also helps controls the cell cycle).

"That is good news, because most cancers are missing p53," Agarwal said.

Finally, the researchers tested the extract in mice. They implanted the animals with advanced human colorectal cancer cells and at the same time, gave the mice grape seed extract through a feeding tube. They tested only one dose, which was larger than a human would comparatively use, Agarwal said, and after eight weeks, tumor volume in treated mice were reduced by 44 percent and tumor weight by percent, compared to control animals. No toxic side effects were observed in treated mice, despite the high doses.

Similar to the cell culture studies, Cip1/p21 protein levels increased in tumors in mice treated with grape seed extract, Agarwal said.

As a first step toward translating their findings into the clinic, the research team now plans to determine the lowest effective, as well as the highest non-toxic doses, by which grape seed extract can offer anticancer benefit in mice.

The study was funded by grants from the National Cancer Institute.


TOPICS: Culture/Society; News/Current Events
KEYWORDS: cancer; colon; coloncancer; grapeseed; grapeseedextract; gse; nutrition; supplements; vitamins
Basically, in both rat and test tube tests, a large dose of grape seed extract over two days killed 92% of all cancer cells. With only one large dose, it decreased tumor size 44% compared with control mice with tumors.

I would give this a try if I had cancer. Get a bottle of 300 from Sam's Club for about $15 and take a bunch over two days. As I understand it, it is GRAS (Generally Recognized As Safe) and the mice had no side effects, either.

More on other grape seed extract studies available at www.activin.com.

1 posted on 11/13/2006 5:32:08 PM PST by ConservativeMind
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To: crabbie; nw_arizona_granny; tmp02

ping


2 posted on 11/13/2006 5:34:54 PM PST by Cindy
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To: ConservativeMind

Good find. I'll be interested to find out more about the biochemistry behind it.


3 posted on 11/13/2006 5:36:34 PM PST by mysterio
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To: ConservativeMind
There's no harm it giving it a try.

I had some grapeseed oil the other day for the first time. (Unrelated to the extract, I suspect). Don't know about any health benefits, but it sure tastes good on pasta and in salads.

4 posted on 11/13/2006 5:36:54 PM PST by Mr. Mojo
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To: ConservativeMind
I can't help but think all the medical advancements over the years due to tests done on mice will result with the mice living longer than humans.
5 posted on 11/13/2006 5:37:27 PM PST by Man50D (Fair Tax , you earn it , you keep it!)
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To: Man50D

All I'm coming up with is a somewhat disturbing mental image of a teensy weensy lower GI.


6 posted on 11/13/2006 5:38:56 PM PST by cripplecreek (If stupidity got us into this mess, then why can't it get us out?)
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To: ConservativeMind

Here is the government GRAS notice:

http://www.foodnavigator.com/news/ng.asp?id=40811-gras-status-for


7 posted on 11/13/2006 5:39:23 PM PST by ConservativeMind
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To: ConservativeMind

Wasn't there a peach pit cure floating around for a while??


8 posted on 11/13/2006 5:41:14 PM PST by Sacajaweau (God Bless Our Troops!!)
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To: ConservativeMind

California merlot bump!


9 posted on 11/13/2006 5:46:25 PM PST by BlazingArizona
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To: mysterio

The complete study this article references is available free, here:

http://clincancerres.aacrjournals.org/current.shtml


10 posted on 11/13/2006 5:49:10 PM PST by ConservativeMind
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To: Man50D

I know you're kidding but I've read that cancer is considered to be cured in mice.


11 posted on 11/13/2006 5:49:51 PM PST by Moonman62 (The issue of whether cheap labor makes America great should have been settled by the Civil War.)
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To: ConservativeMind

I take this. It's also great for hangovers.


12 posted on 11/13/2006 5:54:10 PM PST by spyone
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To: mysterio

The issue this is in is the prior issue. The specific PDF link is here:

http://clincancerres.aacrjournals.org/cgi/reprint/12/20/6194


13 posted on 11/13/2006 5:54:12 PM PST by ConservativeMind
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To: Cindy

Thanks, Cindy, for thinking of me.

I really appreciate any articles like this that you come across. I truly believe that a cure is just around the corner...I just keep praying!


14 posted on 11/13/2006 5:55:30 PM PST by crabbie
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To: Mr. Mojo; ConservativeMind
I had some grapeseed oil the other day for the first time. (Unrelated to the extract, I suspect). Don't know about any health benefits, but it sure tastes good on pasta and in salads.

It's also great for your skin and is used as a 'carrier' oil to retain and distribute other essential oils in organic skin care products. Here's the info I have from my supplier:


Grape seed oil
Grapeseed Oil ( Vitis vinifera ) is an ecologically sound product that is made from the seeds of grapes after the wine is pressed. Grapeseed oil is high in vitamin E and is 76% essential fatty acid, linoleic acid (also known as Omega 6). It is low in saturated fat, contains natural chlorophyll and valuable antioxidants (known as proanthocyninidins), and has a good shelf life. Very rich in vitamins and minerals. It's a light and penetrating oil for massage. It’s also used in lotions, balms, creams, and soap. The skin absorbs it easily; it has no perceptible odor. Since it is slightly astringent, it tightens and tones the skin. Will not aggravate acne. This is one oil that is nearly impossible to extract through cold pressure due to its very low oil yield.

Never thought of eating it, but I may have to give it a try. :-)

15 posted on 11/13/2006 5:56:12 PM PST by MamaTexan (~ There is no such thing as a Big Government Conservative ~)
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To: ConservativeMind

2 glasses of 100 per cent grape juice a day. keeps the doctor away.


16 posted on 11/13/2006 5:58:15 PM PST by zarf
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To: ConservativeMind; glock rocks

Burp for later...


17 posted on 11/13/2006 6:01:46 PM PST by tubebender (Growing old is mandatory...Growing up is optional)
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To: MamaTexan
The oil has benefits, but it appears there may be little of the compound they think might be helping. From Wikipedia:

Some sources claim that grape seed oil is also high in procyanidolic oligomers (also known as oligomeric proanthocyanidins, OPCs or PCOs). However other sources dispute this. Because proanthocyanidins are polar molecules which are insoluble in nonpolar liquids such as oils, grape seed oil is unlikely to contain as much PCO as other grape products like fresh grapes, grape juice or red wine. Some published independent analyses show that grape seed oil typically contains almost no PCO at all [1]. It has been claimed that many distributors of pycnogenol and related products are involved in pyramid schemes [2]. This in no way impacts its possible health benefits, of course.

http://en.wikipedia.org/wiki/Grape_seed_oil
18 posted on 11/13/2006 6:04:13 PM PST by ConservativeMind
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To: zarf

I switched from orange to grape juice. Much smoother taste.


19 posted on 11/13/2006 6:07:06 PM PST by Sacajaweau (God Bless Our Troops!!)
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To: ConservativeMind

"Pinky, are you pondering what I'm pondering?"
"Duh, I think so, Brain...but it's a long way to Napa Valley."


20 posted on 11/13/2006 6:07:15 PM PST by RichInOC (No! BAD Rich!)
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To: ConservativeMind
The oil has benefits, but it appears there may be little of the compound they think might be helping. From Wikipedia:

As to the exact compound, they could be correct. But then again, it is Wikipedia. :-)

Someone with more knowledge on the subject than I will have to judge whether or not it's correct.

But it does work great on the skin!

21 posted on 11/13/2006 6:10:38 PM PST by MamaTexan (~ There is no such thing as a Big Government Conservative ~)
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To: crabbie

And I (like many others) are praying for you everyday, too, crabbie.


22 posted on 11/13/2006 6:16:14 PM PST by Cindy
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To: ConservativeMind

Thanks for the links. I work in biochem.


23 posted on 11/13/2006 6:18:47 PM PST by mysterio
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To: ConservativeMind
Good news. Of course we might want to get it soon, before pharmaceuticals take it off the market like they did shark cartilage. They claimed if can treat cancer it is a medicine and therefore subject to FDA approval.
24 posted on 11/13/2006 7:32:02 PM PST by gidget7 (Political Correctness is Marxism with a nose job)
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To: Cindy

I appreciate the prayers so much more than you could ever imagine...

:-)


25 posted on 11/13/2006 8:21:55 PM PST by crabbie
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To: ConservativeMind

Wow. Thanks for posting this.
Bookmarked.


26 posted on 11/13/2006 8:23:27 PM PST by Lancey Howard
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To: ConservativeMind

BTW, you do realize that this kind of stuff drives the pharmaceutical companies up a wall?
Have they responded with their pooh pooh yet?


27 posted on 11/13/2006 8:24:52 PM PST by Lancey Howard
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To: Lancey Howard
BTW, you do realize that this kind of stuff drives the pharmaceutical companies up a wall?

Oh no, I'm sure they'll love it. They'll remove the compound that works in nature, alter it by one molecule, reduce it's efficiency, add side effects, then patent their new drug. Then they can make more drugs to deal with the side effects.

28 posted on 11/13/2006 8:42:46 PM PST by Marie (Enjoy it Dems. It won't happen next time.)
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To: ConservativeMind; JulieRNR21
Basically, in both rat and test tube tests, a large dose of grape seed extract over two days killed 92% of all cancer cells. With only one large dose, it decreased tumor size 44% compared with control mice with tumors.

Exellent information!

Julie; prayers are daily delivered, please see my e-mail to you regarding Ologomeric Proantho Cyanidins and its ingredients!!

29 posted on 11/13/2006 8:57:04 PM PST by danamco
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To: MamaTexan

Refrigerate it once it is opened. It can turn quickly if left out. I buy it in metal cannisters from a French producer, through Cookswares, and use it on salads and in cooking. I think it's about $8. for 16ounces. Cheap really, and you wind up not using big dollops.

It has a higher heat point than peanut oil, actually than any other oil.

I patted some on a baby visitor with a slight diaper rash since nothing else was available.

I like it because unlike olive oil it doesn't overwhelm the flavors in a salad or other food.

This particular French brand doesn't even seem "oily."


30 posted on 11/13/2006 9:47:04 PM PST by Barset
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To: ConservativeMind; All

okay.....for all your nutrition buffs out there.....does anybody know anything about Zangojuice...???


31 posted on 11/13/2006 9:49:51 PM PST by cherry
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To: crabbie

I know.
Prayer is powerful.


32 posted on 11/14/2006 3:07:00 AM PST by Cindy
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To: Cindy

thanks cindy for the ping


33 posted on 11/14/2006 8:47:10 AM PST by tmp02
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To: crabbie

Me too.


34 posted on 11/14/2006 8:56:18 AM PST by tmp02
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To: ConservativeMind

Bump


35 posted on 12/12/2006 6:22:14 AM PST by houeto (Jacob's enemy is the revitalized end-time beast!)
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To: ConservativeMind

Thank you!
In my last week of radiochemotherapy and will take up GSE immediately thereafter.


36 posted on 12/12/2006 6:33:41 AM PST by G Larry (Only strict constructionists on the Supreme Court!)
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To: ConservativeMind
I've been taking this for years. It comes in both caplets(easier to swallow than capsules) and liquid (extract). In the herbal world it is used as an natural antibiotic. It heals wounds, rashes and is excellent as a cheap replacement for anti-virus spray for your counter tops.

NutriBiotic (the brand I use) claims just a few drops will make any water drinkable.

They also have products such as Bath Gel/Shampoo, Ear drops, skin spray etc.

37 posted on 12/12/2006 7:12:07 AM PST by SweetCaroline (***Your own healing is the Greatest Message of Hope to others!***)
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To: SweetCaroline
Another great product is AHCC. Read up on it here:

http://www.ahccpublishedresearch.com/wwwroot-ahcc/studies/AHCC_02_1002.html

38 posted on 12/12/2006 7:24:33 AM PST by SweetCaroline (***Your own healing is the Greatest Message of Hope to others!***)
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To: SweetCaroline
You may want to re-check your products.

The items Nutibiotic sells are not grape seed extract. They are GRAPEFRUIT seed extract.
39 posted on 12/12/2006 1:49:23 PM PST by ConservativeMind
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