2005-07-14

Potent Spice Works

To Block Growth Of Melanoma In Lab Test

HOUSTON - Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, say researchers from The University of Texas M. D. Anderson Cancer Center.

 
The study, to be published in the August 15, 2005 issue of the journal Cancer, but available on line at 12:01 a.m. (EDT) on Monday, July 11, demonstrates how curcumin stops laboratory strains of melanoma from proliferating and pushes the cancer cells to commit suicide.

It does this, researchers say, by shutting down nuclear factor-kappa B (NF-kB), a powerful protein known to promote an abnormal inflammatory response that leads to a variety of disorders, including arthritis and cancer.

The study is the latest to suggest that curcumin has potent anticancer powers, say the researchers.

"The antioxidant, anti-inflammatory and anti-carcinogenic properties of curcumin derived from turmeric are undergoing intense research here and at other places worldwide," says one of the study's authors, Bharat B. Aggarwal, Ph.D., professor of cancer medicine in the Department of Experimental Therapeutics.

At M. D. Anderson, for example, dramatic results from laboratory studies have led to two ongoing Phase I human clinical trials, testing the ability of daily capsules of curcumin powder to retard growth of pancreatic cancer and multiple myeloma. Another Phase I trial is planned for patients with breast cancer, and given this news of curcumin's activity in melanoma, animal studies will soon begin, Aggarwal says.

Ground from the root of the Curcuma longa plant, curcumin is a member of the ginger family. It has long been utilized in India and other Asian nations for multiple uses: as a food-preservative, a coloring agent, a folk medicine to cleanse the body, and as a spice to flavor food (two to five percent of turmeric is curcumin, for example).

While researchers had thought curcumin primarily has anti-inflammatory properties, the growing realization that cancer can result from inflammation has spurred mounting interest in the spice as an anti-cancer agent, Aggarwal says. He adds that another fact has generated further excitement: "The incidence of the top four cancers in the U.S. - colon, breast, prostate, and lung - is ten times lower in India," he says.

This work is just the latest by M. D. Anderson researchers to show how curcumin can inhibit cancer growth. "Curcumin affects virtually every tumor biomarker that we have tried," says Aggarwal. "It works through a variety of mechanisms related to cancer development. We, and others, previously found that curcumin down regulates EGFR activity that mediates tumor cell proliferation, and VEGF that is involved in angiogenesis. Besides inhibiting NF-kB, curcumin was also found to suppress STAT3 pathway that is also involved in tumorigenesis. Both these pathways play a central role in cell survival and proliferation."

He said that an ability to suppress numerous biological routes to cancer development is important if an agent is to be effective. "Cells look at everything in a global way, and inhibiting just one pathway will not be effective," says Aggarwal.

In this study, the researchers treated three different melanoma cell lines with curcumin and assessed the activity of NF-kB, as well the protein, known as "IKK" that switches NF-kB "on." The spice kept both proteins from being activated, so worked to stop growth of the melanoma, and it also induced "apoptosis," or programmed death, in the cells.

Surprisingly, it didn't matter how much curcumin was used, says the researchers. "The NF-kB machinery is suppressed by both short exposures to high concentrations of curcumin as well as by longer exposure to lower concentrations of curcumin," they say in their study. Given that other studies have shown curcumin is non-toxic, these results should be followed by a test of the spice in both animal models of melanoma and in human trials, they say.

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The study was funded by the National Cancer Institute and the Department of Defense. Co-authors included principle investigator Razelle Kurzrock, M.D.; first author Doris Siwak, Ph.D. and Shishir Shishodia.

http://www.sciencedaily.com/releases/2005/07/050712232338.htm

Spice Up Your Brain

Researchers looking for ways to fight Alzheimer's disease are hopeful that one answer might be found in a simple bowl of curry. That's because curcumin, a compound found in the curry spice turmeric, reduces the buildup of amyloid protein plaque that is associated with the disease.

That could explain why rates of Alzheimer's, which robs people of their memory and their ability to live fully and independently, are among the lowest in the world in India, where the spice is a dietary staple.

In a recent study on rats, scientists found that curcumin significantly reduced the buildup of beta-amyloid protein in the synapses, or gaps, between brain cells. These synapses connect nerve cells and are critical for memory.

Curcumin at work

Curcumin, and turmeric itself, have powerful antioxidant and anti-inflammatory properties, says David Winston, a registered herbalist and dean of the Herbal Therapeutics School of Botanic Medicine in Broadway, New Jersey. According to Winston, scientists already found that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen reduce the risk for Alzheimer's, but not without side effects such as gastric bleeding.

Studies on rats and mice show that curcumin works similarly to NSAIDs but without side effects, reducing brain inflammation and decreasing the oxidized proteins that form harmful plaque. Researchers think the compound will have similar effects in humans.

Dietary antioxidants protect against chronic inflammation and oxidative diseases, says Winston. He recommends that people incorporate a variety of antioxidants into their diet, including turmeric, rosemary and blueberries. Additionally, ginkgo biloba increases circulation and reduces oxidative processes in the brain.

Eating curcumin or turmeric on a regular basis seems to be helpful, but if you don't like it, don't worry. You can take a curcumin or turmeric supplement, says Winston. He prefers turmeric, since it may provide more antioxidant constituents than curcumin. Plus, curcumin can cause stomach irritation in some people, he cautions.

Winston suggests three different ways to get your curcumin...

1. Turmeric capsules. Take two capsules, two to three times a day.
2. Curcumin tincture. Take 3 milliliters (ml) to 4 ml, three times a day.
3. Supplemental curcumin. Take between 1,200 mg and 1,800 mg a day, in three divided doses. Caution: Individuals prone to bleeding or on blood thinners should not take turmeric. Remember to stop using 10 to 14 days before any dental or surgical procedure.

While you're keeping your pathways clean, don't forget to keep your mind active. Research has shown that your brain creates new pathways when you learn something new.

Be well, Carole Jackson, Bottom Line's Daily Health News, Sept/05

CURCUMIN
A Powerful and Natural Cancer-Fightng Substance
The Following is a summary of the Laboratory Studies that are showing Curcumin induces many biological effects that fight the development and proliferation of cancer cells

Suppressing nuclear factor kappa beta (NF-KB). Cancer cells often over-express NF-KB and use this as a means to proliferate. Curcumin has been shown to suppress NF-KB.

Blocking cancer-mimicking chemicals that promote cancer growth. Curcumin blocks estrogen and estogen-mimicking chemicals that promote cell mutation and proliferation. These chemicals are found in our environment and are encounctered daily and include paraquat, a weed killer, notrosamines in cooked and "lunch" meats, carbon tetrachloride (a solvent found in paints and other products).

Suppressing inflammation inherent in certain forms of cancer. Curcumin inhibits cyclooxygenase (COX) and lipoxygebnaise (LOX), two enzymes that promote inflammation believed to play a significant role in the development and progression of cell carcinoma and colon cancer.

A Strong Antioxidant. Curcumin protects our cells against free radicals that promote cancer and cause aging by damaging DNA and activating genes. In a recent laboratory study, curcumin protected bacteria from a lethal dose of radiation almost flawlessly.

Destroying Abnormal Pre-cancerous Cells. Stops certain forms of cancer by inducing "aptosis," a process that identifies cancerous cells and instructs them to self-destruct.

Stopping Cancer Cells from Multiplying. Stops the growth of cancer cells in the advanced stages of cancer development.

Enhancing Immunity Shown to stimulate both localized and general immunity including CD4 + T-helper and By type immune cells.

Inhibiting Angiogenesis, or the process by which tumors create their own blood supply. Curcumin inhibits the enzyme critical to the process and by blocking iron and copper from the bloodstream, which are required for the growth of blood vessels that the tumors require.

References:
1. On tumor cells in a lab dish, curcumin prevents or slows prostate and lung cancer. But dietary consumption of turmeric, researchers report, so far shows no effect on those organs and failed to inhibit tobacco-induced tumors (Cancer Lett 1999 Apr 1;137(2):123-30).

2. Recent studies have found that curcumin has a dose-dependent chemo-preventive effect in rats during promotion/progression stages of colon cancer (Cancer Res 1999 Feb 1; 59(3): 597-601). It has similar preventive effects against skin cancer, oral cancer and forestomach and other intestinal tumors (J Surg Res 2000 Apr; 89(2): 169-75).

3. According to Tufts researchers, "a mixture of curcumin and isoflavonoids is the most potent inhibitor against the growth of human breast tumor cells. These data suggest that combinations of natural plant compounds may have preventive and therapeutic applications against the growth of breast tumors induced by environmental estrogens" (Environ Health Perspect 1998 Dec;106(12):807-12)

4. Turmeric compares with soy, licorice, red clover, and thyme in binding to progestrone and estrogen receptors in breast cancer cells (Proc Soc Exp Biol Med 1998 Mar;217(3):369-78).

4. Kentucky researchers found that curcumin "inhibited proliferation of a variety of B lymphoma cells" (Clin Immunol 1999 Nov;93(2):152-61).

5. Curcumin may or may not protect against cellular damage from radiation, perhaps depending on dose. It appears to protect against damage to certain organs brought about by some chemotherapy agents. In hamsters it protects the kidneys from Adriamycin (Br J Pharmacol 2000 Jan;129(2):231-4). If you are taking radiation or chemotherapy, discuss your diet and use of any antioxidants with your oncologist.

6. Typical dietary amounts of turmeric have an anti-oxidant effect that protects rats from cataracts (Toxicol Lett 2000 Jun 5;115(3):195-204).

7. Curcumin protects rats from liver-damage caused by toxins (J Pharm Pharmacol 2000 Apr; 52(4): 437-40; Carcinogenesis 2000 Feb; 21(2): 331-5)

From:   http://youngagain.com/marcella75/cumin1.html

Curry Spice Could Slow Alzheimer's, Study Shows
By E. J. Mundell

NEW YORK (Reuters Health) - Diets rich in curcumin--a compound found in the curry spice turmeric--may help explain why rates of Alzheimer's disease are much lower among the elderly in India compared with their Western peers.

Alzheimer's disease is characterized by the buildup of amyloid protein ``plaques'' within the brain. In studies in rats, curcumin ``not only reduces the amyloid, but also reduces the (brain's) response to the amyloid,'' according to researcher Dr. Sally Frautschy of the University of California, Los Angeles.

She presented her findings Thursday at the annual meeting of the Society for Neuroscience in San Diego, California.

Previous studies have noted that elderly individuals living in Indian villages appear to have the lowest incidence of Alzheimer's disease in the world, with just 1% of those aged 65 and older contracting the degenerative brain condition. The reasons for this low incidence remain unclear, however.

Frautschy speculated that curcumin found in curry could provide a clue to this puzzle since the compound has ``a long history of dietary and herbal medicinal use'' and is also a powerful antioxidant and anti-inflammatory agent. In her study, Frautschy fed middle-aged (9 months old) and aged (22 months old) rats diets rich in curcumin. All of the rats had received brain injections of amyloid to mimic progressive Alzheimer's disease.

``Curcumin reduced the accumulation of beta-amyloid and the associated loss of proteins'' in the synapses, or gaps, between individual brain cells, Frautschy reported.

``Synapses connect nerve cells and are crucial for memory,'' the California researcher explained. Keeping synapses free of plaque is important because ``their loss correlates well with memory decline in Alzheimer's.'' This type of memory preservation may have been reflected in the fact that rats fed curcumin also performed much better in memory-dependent maze tests compared with rats on normal diets, according to Frautschy. Curcumin also appeared to reduce Alzheimer's-related inflammation in neurologic tissue.

Because ``a combined anti-inflammatory and antioxidant approach will be useful for Alzheimer's prevention or treatment,'' Frautschy speculates that curcumin could be especially valuable in the fight against the disease, especially in combination with anti-inflammatory drugs like ibuprofen. Her team is hopeful they will soon receive funding for clinical trials to investigate curcumin-ibuprofen combination therapy.

Curcumin may not be the only compound in the kitchen spice rack able to ward off Alzheimer's. In an interview with Reuters Health, Frautschy said that ``chemicals from rosemary (rosmarinic acid) and ginger (vanillin and zingerone, also high in Indian diets) have similar structure and should be tested.''

Summary of Study:

The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse.

Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM.

Departments of Medicine and Neurology, University of California, Los Angeles, Los Angeles, California 90095, and Greater Los Angeles Veterans Affairs Healthcare System, Geriatric Research, Education and Clinical Center, Sepulveda, California 91343.

Inflammation in Alzheimer's disease (AD) patients is characterized by increased cytokines and activated microglia. Epidemiological studies suggest reduced AD risk associates with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed inflammation and plaque-related pathology in an Alzheimer transgenic APPSw mouse model (Tg2576), excessive use of NSAIDs targeting cyclooxygenase I can cause gastrointestinal, liver, and renal toxicity. One alternative NSAID is curcumin, derived from the curry spice turmeric. Curcumin has an extensive history as a food additive and herbal medicine in India and is also a potent polyphenolic antioxidant. To evaluate whether it could affect Alzheimer-like pathology in the APPSw mice, we tested a low (160 ppm) and a high dose of dietary curcumin (5000 ppm) on inflammation, oxidative damage, and plaque pathology. Low and high doses of curcumin significantly lowered oxidized proteins and interleukin-1beta, a proinflammatory cytokine elevated in the brains of these mice. With low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP was reduced, and insoluble beta-amyloid (Abeta), soluble Abeta, and plaque burden were significantly decreased by 43-50%. However, levels of amyloid precursor (APP) in the membrane fraction were not reduced. Microgliosis was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component shows promise for the prevention of Alzheimer's disease.

From:   http://youngagain.com/marcella75/cumin.html

 
Curcumin

Curcumin also restores and protects kidney and liver functions
 BRITISH JOURNAL OF PHARMACOLOGY, 2000, Vol 129, Iss 2, pp 231-234

A study investigated the effect of curcumin on artificially induced kidney disease in rats. Results indicated that treatment with curcumin prevented the kidney injury and restored kidney function. Treatment with curcumin significantly protected against proteinuria, albuminuria, hypoalbuminaemia and hyperlipidaemia. Curcumin inhibited the increase in urinary excretion of N-acetyl-beta-D-glucosaminidase (a marker of kidney tubular injury), fibronectin and glycosaminoglycan and blood cholesterol. The data also demonstrated that curcumin protected against kidney injury by suppressing free radicals and increasing kidney glutathione content and glutathione peroxidase activity (endogenous antioxidants). Curcumin also eliminated kidney microsomal and mitochondrial lipid peroxidation. The data suggest that administration of curcumin is a promising approach in the treatment of kidney disease.

Curcumin Concentrated Tumeric Extract is a potent antioxidant with specific antiviral, anti-inflammatory, anti-cancer and cholesterol-lowering effects.

Curcumin is especially recommended for hepatitis C patients. One study found it to be more effective than green tea extract in suppressing viral damage to liver cells. Curcumin induces cancer cell apoptosis or death. Apoptosis can be defined simply as programmed cancer cell death. Cancer researchers are focusing in on agents that induce apoptosis as the next generation of cancer drugs. Many of the nutrients in the cancer treatment protocol such as selenium, vitamin A, green tea and vitamin D3 induce apoptosis.

The most effective nutrient available to induce apoptosis may be curcumin. Curcumin is an antioxidant extract from the spice turmeric that produces a wide range of health benefits. Cancer patients should be taking 2000 mg to 4000 mg a day of curcumin extract with a heavy meal. In a wide range of cancer cells, curcumin has been shown to induce cell shrinkage, chromatin condensation, DNA fragmentation and block cellular signal transduction, all of which are characteristics of apoptosis according to an article published in the journal Nutrition and Cancer USA (26/1 1996).

CURCUMIN
A Powerful and Natural Cancer-Fightng Substance
The Following is a summary of the Laboratory Studies that are showing Curcumin induces many biological effects that fight the development and proliferation of cancer cells

• 
  Suppressing nuclear factor kappa beta (NF-KB). Cancer cells often over-express NF-KB and use this as a means to proliferate. Curcumin has been shown to suppress NF-KB.
• Blocking cancer-mimicking chemicals that promote cancer growth. Curcumin blocks estrogen and estogen-mimicking chemicals that promote cell mutation and proliferation. These chemicals are found in our environment and are encounctered daily and include paraquat, a weed killer, notrosamines in cooked and "lunch" meats, carbon tetrachloride (a solvent found in paints and other products).
• Suppressing inflammation inherent in certain forms of cancer. Curcumin inhibits cyclooxygenase (COX) and lipoxygebnaise (LOX), two enzymes that promote inflammation believed to play a significant role in the development and progression of cell carcinoma and colon cancer.
• A Strong Antioxidant. Curcumin protects our cells against free radicals that promote cancer and cause aging by damaging DNA and activating genes. In a recent laboratory study, curcumin protected bacteria from a lethal dose of radiation almost flawlessly.
• Destroying Abnormal Pre-cancerous Cells. Stops certain forms of cancer by inducing "aptosis," a process that identifies cancerous cells and instructs them to self-destruct.
   
  Stopping Cncer Cells from Multiplying. Stops the growth of cancer cells in the advanced stages of cancer development.
• Enhancing Immunity Shown to stimulate both localized and general immunity including CD4 + T-helper and By type immune cells.
• Inhibiting Angiogenesis, or the process by which tumors create their own blood supply. Curcumin inhibits the enzyme critical to the process and by blocking iron and copper from the bloodstream, which are required for the growth of blood vessels that the tumors require.

Serving size 2 capsules
1000 mg Turmeric root powder standardized*
95% (950 mg) curcumin
Dosage: Healthy people should take one capsule, once or twice daily with meals. 3-4 capsules can be taken 2X daily with meals by people who have cancer or liver problems.

Caution: Always take with meals because curcumin can cause gastric irritation and ulceration if taken on an empty stomach. Do not take curcumin if you have biliary tract obstruction.

For Further Information go to http://youngagain.com/

Dear Reader, A somewhat rare condition might lead researchers to a noninvasive cancer solution for people with a far more common condition: colorectal polyps.

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Years in the making
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Familial adenomatous polyposis (FAP) is a hereditary condition that affects only about 10,000 people in the U.S. FAP patients typically begin to develop numerous benign polyps in the colon when they're only in their teens.

Polyps continue to multiply into the hundreds and sometimes thousands as FAP patients age. Eventually the polyps become malignant, usually when patients reach their 50s. Before malignancy, polyps can be removed during colonoscopy, although this may not be practical with patients who have very high polyp counts. Once malignancy begins, the colon has to be removed.

Nonsteroidal anti-inflammatory drugs and COX-2 inhibitors can sometimes reverse the progression of polyps, but as I've noted in many e-Alerts, these drugs commonly produce harsh adverse side effects when taken on a regular basis.

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Flavorful and pungent
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Previous studies have shown that curcumin produces anti-inflammatory effects that may fight cancer.

Curcumin is a yellow pigment in the root of turmeric, an herb in the ginger family. Curry gets its pungent flavor from curcumin, which was used for many centuries by Indian Ayurvedic healers to treat indigestion, arthritis and urinary tract disorders.

Researchers at Johns Hopkins University School of Medicine recently tested the effects of curcumin and quercetin (a plant flavanoid found in apples and onions) on five FAP patients.

STUDY ABSTRACT

All subjects received supplements containing 480 mg of curcumin and 20 mg of quercetin three times each day for six months
The number and size of polyps were evaluated at the beginning and end of the study
Results showed a 60 percent decrease in the number of polyps, on average
The average size of polyps was reduced by more than 50 percent
About halfway through the study, researchers found that one subject had not been taking his supplements. A check of his polyps showed their number had increased. But after restarting the daily supplement regimen, the number of polyps dropped by the end of the trial period.

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Handle with care
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Johns Hopkins researcher, Francis Giardiello, M.D., told FoodNavigator that the amount of quercetin used in the study was similar to the daily quercetin intake that many people get through a normal diet. But the curcumin intake provided by the supplement was many times higher than the amount of curcumin that could be consumed through dietary intake.

Dr. Giardiello believes that the positive results of the study might be primarily due to the curcumin supplement. He also notes that eating onions and curry won't necessarily produce the same protective effect of supplemental extracts. The Hopkins team is currently planning a large intervention study to further explore the effect of curcumin extract on colon polyps.

Talk to your doctor or a healthcare professional before taking curcumin or quercetin supplements. Although only a few mild side effects were reported in the Hopkins trial, some people experience stomach upset and even ulcers with high doses of curcumin. Also, curcumin is known to thin the blood, so it should not be taken with anti-coagulants or anti-inflammatory drugs.

To Your Good Health, Jenny Thompson

Sources:

"Combination Treatment With Curcumin and Quercetin of Adenomas in Familial Adenomatous Polyposis" Clinical Gastroenterology and Hepatology, Vol. 4, No. 8, August 2006, cghjournal.org

"Curry and Onion Extracts Could Protect Against Colon Cancer" FoodNavigator, 8/2/06, foodnavigator.com
"Teen Cancer Patient's Court Battle Leads to Va. Legislation" Larry O'Dell, The Associated Press, 8/24/06, dailypress.com

August 30, 2006  http://www.hsibaltimore.com/ealerts/freecopy.html

References:

1) Aggarwal BB, Banerjee S, Bharadwaj U, et al. Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines. Biochem Pharmacol. 2007 Apr 1;73(7):1024-32. Epub 2006 Dec 15.

2) Si X, Wang Y, Wong J, et al. Dysregulation of the ubiquitin-proteasome system by curcumin suppresses coxsackievirus B3 replication. J Virol. 2007 Apr;81(7):3142-50. Epub 2007 Jan 17.

3) Natural Standard Research Collaboration: The Authority on Integrative Medicine. [www.naturalstandard.com] Copyright © 2007.