Curcumin
Worldwide clinical trials have chiseled out a definite place for curcumin in oncology. Among them are New York Presbyterian Hospital and the Weill Medical College, which reported that curcumin, a curcuminoid found in turmeric, directly inhibited the COX-2 enzyme (Zhang et al. 1999). So excited are various oncologists regarding curcumin that the potent anti-inflammatory has been classed as a potential third generation cancer chemopreventive agent.

Curcumin inhibited thromboxane A2 (TxA2), a highly unstable, biologically active compound created by COX from AA (Shah et al. 1999; Newmark et al. 2000). Unless controlled, TxA2 promotes tumor endothelial cell migration (metastasis) and angiogenesis. By inhibiting TxA2, curcumin reduces the tumor's blood supply and lessens the threat of metastasis (Arbiser et al. 1998; Nie et al. 2000). Curcumin is effective at inhibiting 5-lipoxygenase and subsequently HETE, a survival factor for prostate, breast, and pancreatic cancers (Ghosh et al. 1998; Ding et al. 1999; Newmark et al. 2000; Li et al. 2001).

The following list illustrates the depth of curcumin's defenses against cancer:

Colon: Curcumin inhibited chemically induced carcinogenesis in the colon when administered at different stages of the cancer process. Laboratory rats, administered curcumin during either initiation or late in the premalignant phase, had a lesser incidence and fewer numbers of invasive malignant colon tumors (Kawamori et al. 1999). Also, by inhibiting COX-2-arachidonic acid interactions, curcumin suppresses prostaglandins responsible for inflammatory processes (Plummer et al. 1999). Chronic inflammation has for decades been regarded as a cause of colon cancer (Konig et al. 1976).
Antioxidant activity: Curcumin inhibits or possibly even reverses oxidative damage by scavenging and neutralizing free radicals. By defusing the hydroxyl and superoxide radicals and breaking oxidative chain reactions, curcumin protects DNA with greater efficiency than lipoic acid, vitamin E, or beta-carotene (Ruby et al. 1995; Ahsan et al. 1999; Li et al. 2001).
Breast cancer: Curcumin inhibits the growth of multiple breast cancer cell lines (Inano et al. 1999), particularly those that result from exposure to environmental estrogens such as chemicals and pesticides (Verma et al. 1998). Also, curcumin, estrogen, and estrogen mimickers gain entry into the cell through the aryl hydrocarbon receptor. Because curcumin competes for entry, it can crowd out damaging materials (Ciolino et al. 1998). According to researchers, curcumin blends well with other cancer inhibitors. For example, a curcumin-isoflavonoid combination suppressed the growth of estrogen receptor-positive cancer cells up to 95% (Verma et al. 1998).
Oral tumors: Curcumin inhibits oral squamous cell carcinoma more effectively than either genistein or quercetin (Ellatar et al. 2000). Only cisplatin, a platinum-based chemotherapy drug, was more effective.
Skin tumors: Curcumin inhibits skin tumors. When applied topically, curcumin reduces skin inflammation and inhibits local swelling (Huang et al. 1997).
Prostate cancer: Curcumin was able to decrease the proliferative potential of androgen-independent prostate cancer cells--and cells of other androgen-dependent cancers--largely by encouraging apoptosis. Moreover, a significant decrease in microvessel density, the sustaining blood supply of a tumor, was also observed (Dorai et al. 2001).
Leukemia: Curcumin-induced apoptotic cell death in promyelocytic leukemia HL-60 cells at concentrations as low as 3.5 mcg/mL (Kuo et al. 1996).
Protein kinase C (PKC) and epidermal growth factors (EGF): Curcumin was proclaimed "potentially useful" in developing anti-proliferative strategies to control tumor growth by suppressing the activity of protein kinase C (PKC) (Korutla et al. 1995). As the activity of PKC is slowed down, tumor proliferation is halted (Lin et al. 1997). PKC transmits signals from the epidermal growth factor receptor (EGF-R), a cycle that ultimately encourages the growth of tumors. Conversely, cancers awaiting EGF stimulation are dealt a severe blow if this pathway is severed. Curcumin blocked the activation of EGF by 90%.
p53 potentiator: Curcumin increases expression of healthy nuclear p53 protein in human basal cell carcinomas, hepatomas, and leukemia cell lines (Jee et al. 1998). Turn to the protocol Cancer: Gene Therapies, Stem Cells, Telomeres, and Cytokines to read more about tumor suppressor genes.
Tumor necrosis factor-alpha (TNF-alpha): Researchers at the University of Kentucky showed that TNF-alpha acts as a catalyst in cytokine production, stimulating interleukin-6 (IL-6) and -8 (IL-8) and activating NF-kB (Blanchard et al. 2001). Curcumin inhibits TNF-alpha, thus blocking TNF-alpha, NF-kB pathways, and the emergence of pro-inflammatory cytokines (Xu et al. 1997-1998; Li et al. 2001; Literat et al. 2001). To read more about proinflammatory cytokines, turn to the protocol Cancer: Gene Therapies, Stem Cells, Telomeres and Cytokines.
Helicobactor pylori: Exposure of gastric epithelial cells to the ulcer-causing bacterium H. pylori (considered a potential gastric and pancreatic carcinogen) induces secretion of IL-8. IL-8 plays a pivotal role in the development of cancer. The more virulent H. pylori, the greater the production of IL-8. H. pylori strains that fail to induce IL-8 secretion do not activate NF-kB, while all IL-8 inducing strains activate the transcription factor. Curcumin is capable of inhibiting NF-kB and completely suppressing IL-8. By restraining essential players in the development of H. pylori, curcumin diminishes the risks of both gastric and pancreatic cancer (Munzenmaier et al. 1997; Stolzenberg-Solomon et al. 2001).
Although the benefits of curcumin are impressive, curcumin is poorly assimilated. This means that while the digestive tract and liver profit, the remainder of the body may be denied benefit. Administering 2000 mg of curcumin showed that very little reached the bloodstream. This dilemma is amendable by adding a small amount of piperine (a component of black pepper) to curcumin, increasing bioavailability by 2000% (Shoba et al. 1998). However, it is possible that piperine in combination with prescription drugs could increase the bioavailability of the drug. Therefore, it is recommended that curcumin (containing piperine) be taken 2 hours apart from prescription medications.

Super Curcumin dosage: Healthy people typically take 900 mg of curcumin each day. Cancer patients often take as much as four 900-mg capsules 3 times a day for a 6- to 12-month period, reducing the dosage thereafter. Individuals with biliary tract obstruction should avoid curcumin because it enhances biliary flow from the liver. High doses of curcumin should not be taken on an empty stomach to protect against gastric irritation.

Note: The question ultimately arises as to whether curcumin is appropriate during chemotherapy. A recent study from the University of North Carolina (Chapel Hill) showed that curcumin reduced the effectiveness of chemotherapy in breast cancer patients by inhibiting reactive oxygen species (Somasundaram et al. 2002). Please refer to the protocols Cancer: Should Patients Take Dietary Supplements? and Cancer Chemotherapy to read more about this study and the advisability of taking curcumin during conventional treatment.

 

RV30


95% CURCUMIN + QUERCETIN
Presentation 60 x 500mg Capsules

Ingredients Curcumin 95% (60%)+Quercetin (40%)

Dosage For cancer patients 10 caps daily to be taken with meals.
For disease management 6 capsules daily with meals.
For prevention 2 x 2 capsules daily with meals.



Biomedical action Anticancer, antioxidant, anti-inflammatory, cholesterol lowering.

Applications Support in alcohol-induced liver diseases, cancers, Crohn's disease.

Indications Anti-oxidant
Anti-malignancy
Cancer Preventative
Liver Restorative
Anti-inflammatory
IBS, Crohn's disease, ulcerative colitis
Rheumatoid Arthritis, Diabetes & increased oxidative stress
Aids in dementia / Alzheimer's Disease
Combine with SILYBININ


Contra-indications Warfarin
Potentiates Dang Gui, Chuan Xiong & Blood thinning herbs
Use with caution in patients with gallstones or gallbladder disease


Combinations Combine with Coolblue-Liver Restorative. Use with A1 Anti malignancy.

Comments The benefits are shown in all stages of cancer formation: initiation, promotion and progression.
Inhibits the formation of cancer causing nitrosamines
Enhances the body's production of cancer fighting compounds such as glutathione
Promotes the liver's proper detoxification of cancer causing compounds
Prevents over production of cyclooxygenase 2 (cox2) *1-5
Curcumin inhibits cancer growth:
Inhibiting epidermal growth factor *4
Inhibiting angiogenesis *5
Inhibiting nuclear factor kappa beta (NF-kb) *4
Increasing expression of the nuclear p53 protein *4
Inhibiting growth promoting enzymes *4
Experimental studies have found curcumin fights tumours arising from prostate, breast, skin, colon, stomach and liver cancers.


CURCUMIN An overview of the good properties of curcumin related to cancer in general, which includes prostate cancer. (some properties are mentioned more than once in the list A to N). References are in square brackets.

A) Curcumin selectively inhibits phosphorylase kinase, a key regulatory enzyme involved in the metabolism of glycogen. This has important implications for the anti-proliferative effects [CUR 4]
B) Curcumin reduces activity of xanthine oxidase [XO] activity, one of the major causative elements in PMA-mediated tumor promotion [CUR 5]
C) Curcumin inhibits epidermal growth factor (EGF) receptor intrinsic kinase activity up to 90% ......, and also inhibited EGF-induced tyrosine phosphorylation of EGF receptors. These findings demonstrate that curcumin is a potent inhibitor of a growth stimulatory pathway, the ligand-induced activation of EGF-R, and may potentially be useful in developing anti-proliferative strategies to control tumor cell growth.[CUR 6, 7]
D) Curcumin induces cell shrinkage, chromatin condensation, and DNA fragmentation, characteristics of apoptosis [CUR 8]
E) Curcumin inhibits protein kinase C (PKC) activity [CUR 8]
F) Curcumin inhibits tyrosine protein kinase activity [CUR 8]

G)Curcumin, Sulindac and PEMC significantly increase the percentage of apoptosis [CUR 9].
H) Curcumin and Genistein show synergistic inhibitory effects on the growth of human breast cancer MCF-7 cells induced by estrogenic pesticides [CUR 10].

I) Curcumin induced cell shrinkage, chromatin condensation, and DNA fragmentation.. [CUR 11].
J) Curcumin significantly reduced membranous protein tyrosine
kinase activity [CUR 11].

K) Curcumin caused a concentration-dependent inhibition of T-cell .. and may have novel adjuvant immunosuppressive properties. [CUR 12]
L) Curcumin inhibits "tyrosine kinase activity" of p185neu and also depletes p185neu. The growth of several breast cancer cell lines was inhibited. [CUR 13, 15]

M) Curcumin and Genistein block TGF-beta 1-induced u-PA expression and migratory and invasive phenotype in mouse epidermal keratinocytes. [CUR 14]
N) Curcumin inhibits tyrosine kinase activity of epidermal growth factor receptor and depletes the protein. Curcumin can induce apoptosis in both androgen-dependent (AD) and androgen-independent (AI). It can interfere with the signal transduction pathways of the prostate cancer cell and prevent it from progressing to its hormone-refractory state. [CUR 16]


QUERCETIN QUERCETIN is widely distributed in the plant kingdom and is the most abundant of the flavonoid molecules. It is found in many often-consumed foods, including apple, onion, tea, berries, and brassica vegetables, as well as many seeds, nuts, flowers, barks, and leaves. It is also found in medicinal botanicals, including Ginkgo biloba, Hypericum perforatum (St. John's Wort), Sambucus canadensis (Elder), and many others. It is often a major component of the medicinal activity of the plant, and has been shown in experimental studies to have numerous effects on the body.


All flavonoids have the same basic chemical structure, a three-ringed molecule with hydroxyl (OH) groups attached. A multitude of other substitutions can occur, giving rise to the many types of flavonoids. Flavonoids often occur in foods as a glycoside, meaning they have a sugar molecule (rhamnose, glucose, galactose, etc.) attached to the center (C) ring. Quercetin is the aglycone (meaning minus the sugar molecule) of a number of other flavonoids, including rutin, quercetrin, isoquercetin, and hyperoside. These molecules have the same structure as quercetin except they have a specific sugar molecule in place of one of quercetin's hydroxyl groups on the C ring, which dramatically changes the activity of the molecule. Activity comparison studies have identified other flavonoids as often having similar effects as quercetin; but quercetin usually has the greatest activity.

Quercetin appears to have many beneficial effects on human health, including cardiovascular protection, anti-cancer activity, anti-ulcer effects, anti-allergy activity, cataract prevention, antiviral activity, and anti-inflammatory effects.

TCM Pattern Activates Blood and Qi, relieves Pain and opens Channels, Clears the Heart and opens the Orifices to promote consciousness.


Action Flavonoids, as a rule, are antioxidants, and a number of quercetin's effects appear to be due to its antioxidant activity. Quercetin scavenges oxygen radicals, inhibits xanthine oxidase, and inhibits lipid peroxidation in vitro. As another indicator of its antioxidant effects, quercetin inhibits oxidation of LDL cholesterol in vitro, probably by inhibiting LDL oxidation itself, by protecting vitamin E in LDL from being oxidized or by regenerating oxidized vitamin E. By itself, and paired with ascorbic acid, quercetin reduced the incidence of oxidative damage to neurovasculature structures in skin, and inhibited damage to neurons caused by experimental glutathione depletion.

Source: University Of Texas M. D. Anderson Cancer Center

Date: 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.

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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.

###
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.