Cataracts: Reduced Risk with Vitamin E, Lutein, Zeaxanthin and Grape Seed Extract

In recent study published in the Archives of Ophthalmology (Arch. Ophthalmol. 2008;126:102-9) gathered from the Women's Health Study, vitamin E and the carotenoid lutein were both found to be associated with a reduced risk of cataracts.

The Women's Health Study (WHS) was a randomized, placebo-controlled trial involving nearly 40,000 women health professionals aged 45 years and older at inception of the study in 1993.

In this recent study gathered from the WHS, the researchers assessed the antioxidant intake (from food and supplements) of 35,551 women and followed them for an average of ten years. They divided the women's intake into 5 groups, ...groups with the lowest intake, to the next highest intake, to the next highest intake, etc. When women with the highest intake of lutein/zeaxanthin (mean intake of 6.7 mg/day) were compared to the group with the lowest intake (mean of 1.2 mg/day) they found an 18% decrease in the risk of cataracts.

Similarly, when women in the highest intake group of vitamin E (mean 262 mg/day, or 390 IU/day; 1 mg alpha-tocopherol = 1.49 IU) were compared to women in the lowest intake group of vitamin E (mean 4.4 mg/day, or 6.5 IU/day), there found a 14% decrease in cataracts.

This study adds to existing observational studies that xanthophyll carotenoids lutein (and its stereo-isomer, zeaxanthin) may delay cataract formation. (BTW, in animal studies, grape seed extract has been found to reduce the formation of cataracts as well.) Lutein and zeaxanthin concentrate in the tissues of the eye, ...including the lens and retina.

Personally, I take a broad spectrum multi-antioxidant and minerals in chelated form, fish oil, grape seed extract, and additional lutein/zeaxanthin and bilberry extract supplement (for a total lutein intake of 13 mg per day, ...well above the mean intake of the top fifth group of this study). In addition, I take an additional vitamin E supplement, that has the full family of vitamin E (d-alpha tocopherol, d-gamma tocopherol, delta tocopherol, and the tocotrienols), for a combined total of 600 IU/day.

For optimal eye health of the lens and retina (macular degeneration is the number one cause of blindness after the age of 40), as well as maintaining health in a time of increasing risk of chronic degenerative disease, I recommend an optimal intake of various antioxidants, vitamins, minerals, and essential fatty acids.

Posted by Ladd McNamara at 9:05 AM

Effects of Grape Seed Extracts

Human case reports and results from some laboratory and animal studies appear to show that grape seed extract may help to prevent and treat heart diseases such as high blood pressure and high cholesterol. By limiting oxidation, antioxidants in grape seed extract may help prevent changes, including damage to blood vessels, that may contribute to the development of heart disease. Substances in grape seed extract may also block the effects of enzymes that process fats, including cholesterol, from the diet. Consequently, less fat may be absorbed and more may be eliminated from the body. Other research shows that grape seed extract may help to prevent or control damage to body cells that is caused by drugs, pollution, tobacco, and other toxins. While all of these studies appear promising, much more research including long-term studies in humans is needed to confirm initial findings.

Proanthocyanidins are also believed to block the deterioration of blood vessels, therefore, grape seed extract may improve conditions involving veins and arteries. It has been used to prevent, delay, and treat a condition known as chronic venous insufficiency, which occurs when valves in the veins that carry blood back to the heart are weak or damaged. The blood that collects in the veins of the legs can lead to varicose veins, spider veins, or sores on the legs. Results that are more serious may include blood clots in the legs or sores that do not heal and may become infected. This blood vessel strengthening effect of grape seed extract may also help to prevent and treat hemorrhoids.

Since proanthocyanidins in grape seed extract strengthen the walls of all blood vessels, they may also help to keep damaged, stretched, or stiff blood vessels from leaking. In one area of research, grape seed extract may be effective for slowing retinopathy, the gradual break down of the retinas in the eyes, usually due to blood vessel damage. Individuals with arteriosclerosis (a build up of fatty deposits in the arteries), diabetes, or other conditions that increase the likelihood for damage to the small blood vessels in the eyes are more likely to have serious vision problems as a result of that damage. Grape seed extract may also reduce eye stress caused by bright lights. In studies of laboratory animals, it has shown some possible effectiveness in preventing cataract formation, but further study is needed to determine whether this effect may pertain to humans.

One of the polyphenols contained in grape seed extract is called resveratrol. In laboratory and animal studies, resveratrol from grape seeds has appeared to interfere with cancer cell growth and division, as well as causing some cancer cells to disintegrate faster than they would ordinarily. In addition, it may also block enzymes that prolong the survival of several cancer cell types, including skin cancer, prostate cancer, and breast cancer. As a result, tumors may either stop growing or actually shrink because higher than usual numbers of cancer cells die. Therefore, resveratrol may have direct anticancer activity. It may also increase the effectiveness and/or lower the side effects of drugs currently used for cancer chemotherapy. One possible result is that taking resveratrol during chemotherapy may allow lower doses of cancer drugs to be effective, thereby limiting the potential for debilitating side effects. A similar effect was seen in laboratory studies of grape seed extract against HIV, the virus that causes AIDS. Although the exact ways that grape seed extract may fight HIV and other viruses are not known, it is thought that grape seed extract interferes with viral multiplication, possibly by preventing viral attachment to host cells. How high doses of resveratrol and other chemicals in grape seed extract may affect normal human cells is not yet known.

Grape seed extract may also have topical uses. In preliminary research, grape seed extract appears to be moderately effective for preventing tooth decay. It is believed to delay or stop the breakdown of sugars in the mouth and also to inhibit the growth of certain oral bacteria that may play a role in forming dental cavities. In other studies, injuries to the skin of laboratory animals may have healed better when grape seed extract was applied. Through several possible effects that include promoting the regrowth of connective tissues, grape seed extract is believed to encourage faster, stronger healing with less scarring.

Oil pressed from grape seeds is used as a dietary supplement. It contains a relatively high percentage of linoleic acid, which belongs to a group of nutrients known as essential fatty acids (EFAs). The body needs EFAs to regulate activities that include heart function, insulin utilization, and mood balance. However, the body cannot produce EFAs, so they must be obtained from foods or dietary supplements. EFAs are thought to block the production of chemicals that promote the formation of deposits in the blood vessels. Consequently, blood pressure and blood cholesterol levels may be lowered and the risk of heart disease may decrease. Additional studies are needed to confirm the effects of both linoleic acid and grape seed oil for lowering the risk of heart disease.

From article by Wikipedia

http://en.wikipedia.org/wiki/Grape_seed_extract

Study Shows Grape Seed Extract May Be Effective In Reducing Blood Pressure

ScienceDaily (Mar. 27, 2006) — Grape seed extract lowered the blood pressure of patients who participated in a UC Davis study of the benefits of the supplement on people with high blood pressure.

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Conducted by UC Davis cardiovascular researchers, the study was the first human clinical trial to assess the effect of grape seed extract on people with metabolic syndrome, a combination of risk factors that increase the risk for heart disease, including high blood pressure, excess abdominal body weight, high blood cholesterol fats and high blood sugar. The researchers will present the results at the American Chemical Society Meeting and Exposition on March 26 in Atlanta, and at the Federation of American Societies for Experimental Biology's 2006 meeting in San Francisco April 2.

It is estimated that 40 percent of American adults, or 50 million people, have metabolic syndrome.

The one-month study involved 24 male and female patients diagnosed with metabolic syndrome. The patients were divided into three groups of eight. The first group received a placebo, while the second and third groups received 150 milligrams and 300 milligrams, respectively, of a new grape seed extract. All participants' blood pressure was automatically measured and recorded for 12 hours after ingestion.

"Participants in the two groups receiving grape seed extract experienced an equal degree of reduced blood pressure. The average drop in systolic pressure was 12 millimeters. The average drop in diastolic pressure was 8 millimeters," said the study's lead researcher, C. Tissa Kappagoda, professor of cardiovascular medicine and director of the Preventive Cardiology Program at UC Davis.

Kappagoda adds that the group taking 300 milligrams of grape seed extract also had reduced serum oxidized LDL cholesterol levels.

"Generally, the higher their initial oxidized LDL level was, the greater the drop by the end of the study," he said. The extract has received the GRAS (generally recognized as safe) certification from the FDA and has no known side effects.

The UC Davis research team recently has recently embarked on a second placebo-controlled human clinical study of grape seed extract, looking at its benefits for pre-hypertension patients with systolic pressure of 120-139 mmHg, and diastolic blood pressure of 80-89 mmHg. Three previous studies in animal models by this team have indicated that grape seed extract may also prevent atherosclerosis.

Polyphenolics, a division of Constellation Wines U.S., Inc., funded and supplied the grape seed extract for the study.

Adapted from materials provided by University of California, Davis - Health System.

Grape Seed Extract Help Speed Up Wound Recovery, Study Suggests

ScienceDaily (Dec. 4, 2002) — COLUMBUS, Ohio – Grape-seed extract may help skin wounds heal faster and with less scarring, a new study suggests.

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The extract seemed to aid wound healing in two ways: It helped the body make more of a compound used to regenerate damaged blood vessels, and it also increased the amount of free radicals in the wound site. Free radicals help clear potentially pathogenic bacteria from a wound.

In two related experiments, the researchers tested the effects of grape-seed extract on mice and on human skin cells. It's the first evidence suggesting that a natural extract could have such a profound effect on wound healing, said Chandan Sen, a study co-author and director the Laboratory of Molecular Medicine at Ohio State University's Heart and Lung Research Institute.

"We saw the healing effects grape-seed extract had on wounds from day one," said Sen, who is also an assistant professor of surgery at Ohio State. "It seemed to enhance the formation of epidermal tissue as well as the deposition of connective tissue."

The researchers treated skin wounds on mice with a topical formulation of grape seed proanthocyanidin extract (GSPE). Proanthocyanidin, one of the main ingredients in grape-seed extract, is thought to be a potent antioxidant. But in a wound site, which is rich in free radicals, the extract assumes some pro-oxidant properties.

The study appears in a recent issue of the journal Free Radical Biology and Medicine.

Each of nine mice in the study was given two small puncture wounds on its back. The researchers applied GSPE to one of the wounds, and covered the other with saline solution as a control. Otherwise, the wounds were left to heal naturally.

The animals were euthanized five days after they were wounded. A small area of skin – 1 to 1.5 millimeters – was excised from the edges of the treated and untreated wounds. The researchers looked for signs of enhanced healing in the GSPE-treated samples, and compared these samples to the healing patterns of the saline-treated tissue.

"The skin treated with grape-seed extract was further along in the healing process compared to the saline-treated tissue," Sen said. "The extract-treated skin showed signs of healing faster and the newly formed tissue was denser, meaning that its structure was stronger."

The researchers saw increased levels of tenascin, a protein that helps build connective tissue, in the granulation tissue of the wounds treated with GSPE. Granulation tissue is the rough, pinkish tissue that normally forms as a wound heals. It contains new capillaries and connective tissue.

"Tenascin is a marker for skin wound healing," Sen said. "There was much more tenascin present in the granulation tissue of the wounds treated with GSPE."

The researchers also noted increased levels of VEGF, the compound that helps the body rebuild blood vessels. In previous research, Sen and his colleagues found that GSPE helped turn on the gene responsible for initiating the making of VEGF.

In a related experiment, the researchers also treated human skin cells with GSPE, finding that the extract helped the laboratory-grown cells produce more VEGF.

"More VEGF means blood vessels will form faster and that more nutrients will be carried by the blood to regenerate damaged tissue," Sen said.

In addition to helping blood vessels regenerate, GSPE also seemed to increase free radical levels at the wound site. It may seem odd that an antioxidant could help oxidation – the formation of free radicals – flourish. But

"The extract assumed a mild pro-oxidant property while in an oxidant-rich environment," Sen said. "Excessive amounts of free radicals are damaging. But every living cell makes free radicals. In controlled amounts, they help the body function."

At low concentrations, free radicals can stimulate the proliferation of cells as well as the formation of connective tissue and new blood vessels, Sen said.

"Skin wounds are rich in free radicals," he said. "There was a longer-lasting free radical effect in the wounds that had been treated with grape-seed extract. We think that's partly why these wounds healed faster and better."

While grape-seed extract is good news for wounded tissue, topical grape seed extract isn't sold commercially. And consumers shouldn't expect to get the same wound-healing benefits from taking grape-seed extract in vitamin form, Sen said.

"Taken orally, the extract functions like an antioxidant," he said. "But in a wound, where free radicals are abundant, that proanthocyanidin assumes pro-oxidant behavior."

A grant from the National Institutes of Health supported the work. InterHealth Nutraceuticals, Inc. supplied the grape-seed proanthocyanidin extract for this study.

Sen co-authored the study with Savita Khanna, Sashwati Roy, Nidhi Sharma and Prashant Trikha, all with Sen's Laboratory of Molecular Medicine at Ohio State's Heart and Lung Research Institute; Mika Venojarvi, who is also with Sen's laboratory as well as the University of Kuopio, Finland; and Debasis Bagchi and Manashi Bagchi, who are both with Creighton University Medical Center in Omaha, Neb.

Co-author Debasis Bagchi is also vice president of research and development at InterHealth Nutraceuticals, Inc. and co-author Manashi Bagchi works for the company as well.

Adapted from materials provided by Ohio State University.

Grape Seed Extract Suppresses Estrogen in Breast Cancer
Results may lead to new therapies that target estrogen Contact: Shawn Le 800-888-5323 sle@coh.org DUARTE, Calif., June 1, 2006--Scientists at City of Hope have discovered that chemicals in grape seed extract (GSE) in the form of skin, seeds and even red wine, can suppress the production of estrogen, a major player in the development of breast cancer. GSE can also act specifically upon cancerous breast tissue alone, which produces excess amounts of estrogen, without inhibiting critical estrogen production from healthy tissue. The findings could eventually lead to a preventative therapy that would help both pre- and post-menopausal women. The research, by Shiuan Chen, Ph.D., director and professor, Department of Surgical Research, Ikuko Kijima, a fourth year graduate student at City of Hope’s Graduate School of Biological Sciences, and colleagues, is reported in the June issue of the journal Cancer Research. It follows earlier work by Chen that showed GSE can inhibit the activity of estrogen. With the exception of non-melanoma skin cancers, breast cancer is the most common cancer among women. Approximately 70 percent of all breast cancers are estrogen driven. For years, researchers have targeted aromatase, an enzyme that converts androgen to the female hormone estrogen. While aromatase is normally expressed in a number of tissues such as ovary, placenta, fat and bone, aromatase is expressed at higher levels in breast cancer tissue than normal breast tissue. In the December 2003 Cancer Research, Chen’s lab identified a chemical compound purified from red wine called procyanidin dimers. It proved to be a powerful inhibitor of aromatase activity and also reduced tumor growth in a mouse model. Now the researchers have gone a step further and have shown that GSE can stop breast cancer cells from making the aromatase protein. “We have demonstrated that grape seed extract can have a dual effect,” said Chen. “It can suppress aromatase activity, as well as its expression.” Importantly, the researchers’ work demonstrates this suppression may be targeted to cancerous tissue. This is key to developing future preventative treatment, particularly for pre-menopausal women. While aromatase inhibitors are very effective in suppressing estrogen formation, patients have also experienced side effects associated with estrogen deficiency, such as bone loss. That is because current aromatase inhibitors suppress estrogen in the whole body. The goal of researchers like Chen is to design treatment strategies that selectively suppress aromatase expression in breast tumor tissue while maintaining estrogen levels in normal tissues. The discovery by Kijima, Chen and colleagues that GSE does indeed suppress aromatase expression in breast tumors suggests there are chemicals (not necessarily procyanidin dimers) in GSE that do this, and thus may ultimately be developed as a cancer therapeutic. “We believe these are exciting results because they demonstrate that GSE may be potentially useful in both the treatment as well as the prevention of hormone-dependent breast cancer,” said Chen. Chen said his lab’s ongoing work is to identify the chemicals in GSE that are involved in suppressing estrogen, develop therapeutic drugs based on these chemicals, and eventually go to clinical trials for pre-menopausal women. About City of Hope City of Hope is a leading research and treatment center for cancer, diabetes and other life-threatening diseases. Designated as a Comprehensive Cancer Center, the highest honor bestowed by the National Cancer Institute, and a founding member of the National Comprehensive Cancer Network, City of Hope’s research and treatment protocols impact care throughout the nation. Founded in 1913, City of Hope is a pioneer in the fields of bone marrow transplantation and genetics and shares its scientific knowledge with medical centers locally and globally, helping patients battling serious diseases. For more information, visit www.cityofhope.org.

UC DAVIS STUDIES SHOW THAT GRAPE SEED EXTRACT MAY INHIBIT ARTERY HARDENING

June 27, 2005

(SACRAMENTO, Calif.)— Adding grape seed extract to the diet may prevent atherosclerosis, according to three studies conducted by cardiovascular researchers at UC Davis School of Medicine and Medical Center. The studies, which were presented at the Experimental Biology Conference in San Diego in April, reinforce previous research findings on the beneficial effects of grape seed extract on cardiovascular health.

"Grape seed extract is a powerful antioxidant and has a significant effect on atherosclerosis," says C. Tissa Kappagoda, professor of cardiovascular medicine at UC Davis. "Atherosclerosis, or hardening of the arteries, occurs when cholesterol builds up in artery walls, limiting the ability of the arteries to expand and contract as blood passes through them. Our studies on guinea pigs found that grape seed extract keeps cholesterol from accumulating in the arteries."

In two of the studies, guinea pigs were used to compare the cholesterol accumulation caused by high-fat diets to those resulting from high-fat diets supplemented with grape seed extract. After 12 weeks, the cholesterol accumulation in the animals' tissues was significantly lower in the group that received the grape seed extract.

Results of the third study, done in-vitro, showed that fatty acids found in coconut oil, which generally contribute to atherosclerosis, had an inhibitory effect on endothelial function in rabbit aortas. Grape seed extract reversed this effect.

The grape seed extract used in this experiment contains an oxygen radical absorbance capacity, or ORAC value, 1,000 times higher than that of grape juice. ORAC is a standardized test adopted by the U.S. Department of Agriculture to measure the total antioxidant potency of foods and nutritional supplements.

Polyphenolics, a division of Constellation Wines U.S. and a leading manufacturer of ingredients for the nutritional and beverage industries, funded the research. Its extracts are produced in Constellation Wines U.S. wineries in California from unfermented grapes, using a patented, solvent-free, water extraction process.

For more information, visit www.polyphenolics.com.

Unique Grape Skin Extract Inhibits Prostate Cancer Cell Growth in the Laboratory

Laboratory experiments show that an extract of the skin of muscadine grapes can inhibit growth of prostate cancer cells in the laboratory. Investigators from the National Cancer Institute (NCI), part of the National Institutes of Health, and their research partners also show that muscadine grape skin extract (MSKE) does not contain significant amounts of resveratrol, another grape skin component that has been widely studied and shown to be of potential benefit in preventing prostate cancer growth. The results appear in the September 1, 2007, issue of Cancer Research.

Using a series of human prostate cancer cells, representing different stages of prostate cancer progression, the researchers showed that MSKE significantly inhibits the growth of cancerous, but not normal, prostate cells, primarily by inducing a process called apoptosis, or programmed cell death. Programmed cell death is one of the mechanisms the body uses to rid itself of cells with unrepaired genetic damage before those cells can duplicate themselves. In contrast, resveratrol seems to act by blocking the cell cycle, a sequence of steps that a cell passes through when it grows and divides into two identical cells. Both mechanisms are used by the body to prevent the development of cancer.

According to Jeffrey E. Green, M.D., chief of the Transgenic Oncogenesis and Genomics Section in NCI's Center for Cancer Research (CCR), "These results show that MSKE may have potent antitumor activities in the lab that differ from the effects of resveratrol. Further studies of MSKE will be necessary to determine if this extract has potential as a chemopreventive or therapeutic agent."

The fact that all of the cells studied, which cover the different stages of prostate cancer tumor progression, responded to MSKE suggests that the active compounds in this extract may inhibit tumor development at very early stages.

The muscadine grape (Vitis rotundifolia) is distinct from the more common red grapes used to produce red wines, a major source of resveratrol. The chemical constituents of muscadine grapes differ from most other grape varieties, as they are richer in chemicals called anthocyanins. Anthocyanins, which produce the red and purple colors of the grapes, have strong antioxidant activity and have shown several antitumor effects, including inhibition of DNA synthesis in breast cancer cells, of blood vessel growth in some tumors, and of enzymes involved in tumor spread. Muscadine grapes can be found growing wild from Delaware to the Gulf of Mexico and westward from Missouri to Texas.

While previous studies suggested that anthocyanins might suppress the cancer process, no rigorous study of the mechanisms underlying these effects has yet been done. Resveratrol, by contrast, has been widely examined. Although earlier studies showed that it can induce programmed cell death in prostate cancer cells, resveratrol did not significantly induce cell death in the prostate cell model system used for this muscadine study. The results of this study suggest that resveratrol may activate different antitumor mechanisms than MSKE.

Even though MSKE had significant inhibitory effects on the prostate cancer cells studied, it did not alter the growth rate of the normal human prostate cells in the lab, which served as controls. Ongoing studies of MSKE in animals will help to determine the underlying mechanisms of MSKE's inhibitory effects in prostate cancer cells. The researchers hope that the lab effects of MSKE will be reproducible in testing on cancerous and normal prostate cells in animals. Should MSKE move on to trials in humans, Green says that since "muscadine grape products, including grape juice and grape wine, have been used in human studies without reported side effects, they may be relatively safe for use in clinical trials."

For more information about cancer, please visit the NCI website at www.cancer.gov, or call NCI's Cancer Information Service at 1-800-4 CANCER (1-800-422-6237).

For more information on Dr. Green's research at NCI, please go to http://ccr.cancer.gov/staff/staff.asp?profileid=5721.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Grape Seed Extract Halts Cell Cycle, Checking Growth Of Colorectal Tumors In Mice

ScienceDaily (Oct. 29, 2006) — 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.

Adapted from materials provided by American Association for Cancer Research.