Red Wine To Overcome Tumor Resistance?

They found that very high doses of antioxidant polyphenols shut down and prevent cancerous tumors by cutting off the formation of new blood vessels needed for tumor growth. Polyphenols are commonly found in red wine.

The next cancer drug might come straight from the grocery store, according to new research published in the November 2007 issue of The FASEB Journal. In the study, French scientists describe how high and low doses of polyphenols have different effects. Most notably, they found that very high doses of antioxidant polyphenols shut down and prevent cancerous tumors by cutting off the formation of new blood vessels needed for tumor growth. Polyphenols are commonly found in red wine, fruits, vegetables, and green tea.

At relatively low doses, the French researchers found that the same polyphenols play a beneficial role for those with diseased hearts and circulatory systems by facilitating blood vessel growth. The amount of polyphenols necessary for this effect was found to be the equivalent of only one glass of red wine per day or simply sticking to a healthy diet of fruits and vegetables containing polyphenols.

http://www.fasebj.org/cgi/content/abstract/21/13/3511

In a recent study published in the British Journal of Cancer, phenolics contained in wine possess antioxidant and antimutagenic properties. However, it says that the alcohol itself rather than a particular type of drink is responsible for the reduction in risk.

Polyphenols found in red wine - such as resveratrol - are thought to have anti-oxidant or anti-cancer properties. Polyphenols are antioxidant compounds found in the skin and seeds of grapes. When wine is made from these grapes, the alcohol produced by the fermentation process dissolves the polyphenols contained in the skin and seeds. Red wine contains more polyphenols than white wine because the making of white wine requires the removal of the skins after the grapes are crushed.

http://www.reuters.com/articlePrint?articleId=USROB473874200

What makes these two studies interesting in cancer is the anti-angiogenic enhancer and potentiator effect of the alcohol in red wine. What it seems to tell us is that alcohol reduces the angiogenic secretions by the tumor cells. If it does that, it could both reduce these secretions and make an anti-angiogenesis drug less resistant to the tumor cells, making it more effective. In the presence of an anti-angiogenesis drug, you can have a lethel 1-2 combination which knocks out the new blood vessels which are dependent for survival of the cancer. Polyphenols extracted from red wine could be converted into a pill that is highly likely to be safe, relatively easy and inexpensive to create, and deliver.

Resveratrol is a type of polyphenol called a phytoalexin, a class of compounds produced as part of a plant's defense system against disease. It is produced in the plant in response to an invading fungus, stress, injury, infection or ultraviolet irradiation. Red wine contains high levels of resveratrol, as do grapes, raspberries, peanuts and other plants.

Resveratrol has been shown to reduce tumor incidence in animals by affecting one or more stages of cancer development. It has been shown to inhibit growth of many types of cancer cells in culture. Evidence also exists that it can reduce inflammation. It also reduces activation of NF kappa B, a protein produced by the body's immune system when it is under attack. This protein affects cancer cell growth and metastasis. Resveratrol is also an antioxidant.

Many of the new gene-targeted drugs do not target enough genes. Cancer researchers now recognize hundreds if not thousands of genes must be down-regulated to conquer cancer. In one study, for example, at least 74 genes must be controlled in renal cancer alone (Cancer Biol Ther. 2004 Sep;3(9):889-90. Epub 2004 Sep 24). So-called promiscuous gene inhibitors must be found. A targeted drug like Sutent only down-regulates a small number of genes.

Resveratrol favorably switches many genes, and this has been shown in a renal cancer cell line (PMID: 15467424)(BMC Urol. 2004 Jun 22;4:9). It appears that resveratrol can target "all" genes involved in cancer. It is possible that it also chemosensitizes tumor cells, all the genes within the cell (a potentiator of chemotherapy drugs).

the only negative is that wine has sugar in it and cancer feeds on sugar!  not worth drinking the red wine when you can get the same effect more from a pill form,  also it has sulfates (unless u get organic and sulfate free wine)

Polyphenols found in red wine (resveratrol) are thought to have anti-oxidant and anti-cancer properties. Polyphenols are antioxidant compounds found in the skin and seeds of grapes. When wine is made from these grapes, the alcohol produced by the fermentation process dissolves the polyphenols contained in the skin and seeds. Red wine contains more polyphenols than white wine because the making of white wine requires the removal of the skins after the grapes are crushed, making an anti-angiogenic enhancer and potentiator effect of the alcohol in red wine.

What alcohol does is to reduce the secretion of VEGF by the tumor cells. It both reduces VEGF (blood vessels are dependent on VEGF for survival) and makes anti-antiogenesis drugs work better, possibly overcoming tumor resistance to the drugs.

For an anti-angiogenesis effect, it would be necessary to drink a bottle of wine per day, an amount considered unhealthy. A better option would be polyphenols extracted and converted into a tablet. It takes modern science to isolate the pure compound, test it in the lab, and to go on from there to find new agents to fight disease.

The use of polyphenols as therapeutic tools presents important advantages, because they have a good safety profile, a low cost and they can be obtained everywhere on the planet. Except, big pharma would like to develop, patent, get it's good housekeeping seal of approval from a population study clinical trial to establish it as the "standard," and make millions of bucks to boot! While all the while, something like alcohol can do the same exact thing.

Rochester researchers showed for the first time that a natural antioxidant found in grape skins and red wine can help destroy pancreatic cancer cells by reaching to the cell's core energy source, or mitochondria, and crippling its function. The study is published in the March edition of the journal, Advances in Experimental Medicine and Biology.

The study also showed that when the pancreatic cancer cells were doubly assaulted -- pre-treated with the antioxidant, resveratrol, and irradiated -- the combination induced a type of cell death called apoptosis, an important goal of cancer therapy.

The research has many implications for patients, said lead author Paul Okunieff, M.D., chief of Radiation Oncology at the James P. Wilmot Cancer Center at the University of Rochester Medical Center.

Although red wine consumption during chemotherapy or radiation treatment has not been well studied, it is not "contraindicated," Okunieff said. In other words, if a patient already drinks red wine moderately, most physicians would not tell the patient to give it up during treatment. Perhaps a better choice, Okunieff said, would be to drink as much red or purple grape juice as desired.

Yet despite widespread interest in antioxidants, some physicians are concerned antioxidants might end up protecting tumors. Okunieff's study showed there is little evidence to support that fear. In fact, the research suggests resveratrol not only reaches its intended target, injuring the nexus of malignant cells, but at the same time protects normal tissue from the harmful effects of radiation.

"Antioxidant research is very active and very seductive right now," Okunieff said. "The challenge lies in finding the right concentration and how it works inside the cell. In this case, we've discovered an important part of that equation. Resveratrol seems to have a therapeutic gain by making tumor cells more sensitive to radiation and making normal tissue less sensitive."

Resveratrol is known for its ability to protect plants from bacteria and fungi. Purified versions have been described in scientific journals as potential anti-cancer, anti-inflammatory and anti-atherogenic agents, and for their ability to modulate cell growth. Other well-known antioxidants derived from natural sources include caffeine, melatonin, flavonoids, polyphenols, and vitamins C and E.

A flurry of antioxidant studies in recent years has not proven how and why they work at the cellular level. At the suggestion of a young scientist in his lab, Okunieff began studying resveratrol as a tumor sensitizer. That's when they discovered its link to the mitochondria.

The discovery is critical because, like the cell nucleus, the mitochondria contains its own DNA and has the ability to continuously supply the cell with energy when functioning properly. Stopping the energy flow theoretically stops the cancer.

Researchers divided pancreatic cancer cells into two groups: cells treated without resveratrol, or with resveratrol, at a relatively high dose of 50 mg/ml, in combination with ionizing radiation. (The resveratrol concentration in red wine can be as high as 30 mg/ml, the study said, and higher doses are expected to be safe as long as a physician is monitoring.)

They evaluated the mitochondria function of the cells treated with resveratrol, and also measured apoptosis (cell death), the level of reactive oxygen species in the cells, and how the cell membranes responded to the antioxidant.

Laboratory experiments showed that resveratrol:

* Reduced the function of proteins in the pancreatic cancer cell membranes that are responsible for pumping chemotherapy out of the cell, making the cells chemo-sensitive.

* Triggered the production of reactive oxygen species (ROS), which are substances circulating in the human body that have been implicated in a number of diseases: when ROS is increased, cells burn out and die.

* Caused apoptosis, which is likely the result of increased ROS.

* Depolarized the mitochondrial membranes, which indicates a decrease in the cell's potential to function. Radiation alone does not injure the mitochondrial membrane as much.

The team also wanted to investigate why pancreatic cancer cells seem to be particularly resistant to chemotherapy. The pancreas, a gland located deep in the abdomen, produces insulin and regulates sugar, and pumps or channels powerful digestive enzymes into the duodenum. This natural pumping process, however, ends up ridding the needed chemotherapy from cells in the pancreas. But just as reseveratrol interferes with the cancer cells' energy source, it also may decrease the power available to pump chemotherapy out of the cell.

"While additional studies are needed," Okunieff said, "this research indicates that resveratrol has a promising future as part of the treatment for cancer."

In the same journal, Okunieff and his group also reviewed why resveratrol protects normal tissue, and found that antioxidants can be designed to take advantage of certain biochemical properties or cellular targets, making them more effective.

University of Rochester Medical Center

http://www.urmc.rochester.edu/