by John C. Martin
Imagine if the key to disease prevention was as close as your kitchen shelf. It's not the product of someone's imagination, but the product of years of medical research. Scientists are beginning to take notice of a well-known spice as a potent new preventive therapy against disease, especially cancer.
Cancer takes the lives of more than 1,500 people a day—over 5 million since 1990—and is the second leading cause of death in the United States.(1)
While those statistics are staggering, the medical community is maintaining its focus on mechanisms behind the disease and discovering new, potentially effective methods of treating it. A similar emphasis is placed on prevention, as more and more scientists attempt to uncover the mystery behind ‘carcinogenesis,' particularly at the genetic level.
What is drawing the attention of medical oncologists and researchers these days is a substance known as curcumin, a naturally occurring yellow pigment found in the spice tumeric, which is part of the ginger plant family. Tumeric is widely consumed in its countries of origin not only as a spice, but as a medicine for the treatment of a variety of illnesses. It was long ago used as an anti-inflammatory among Indian practitioners.(2)
Today, curcumin is showing a much broader potential. Not only does the extract work as an antioxidant and anti-inflammatory, but a series of studies in the past four years, focusing on cancer at the cellular level, reveals some exciting findings. For one thing, research is discovering that curcumin is a powerful carcinogenic inhibitor, slowing cancerous cell proliferation by inducing apoptosis, a pre-programmed set of processes within a cell that results in its death.Curcumin Targets Cancer Proliferation
In two recent studies, scientists at New York's Columbia University researched curcumin's therapeutic potential against prostate cancer. In one case last year, the scientists discovered that curcumin had a powerful ability to induce apoptosis and inhibit prostate cell proliferation in vitro by interfering with the cells' protein signaling pathways that typically begin the growth process.(3) Just recently, the researchers extended those findings to determine if they could achieve similar results in an animal model.(4) In their latest study, the researchers found that prostate cancer cells that had been injected subcutaneously into mice, which had been fed a diet of 2% curcumin for six weeks, were unable to develop extensively and underwent significant apoptosis. "Curcumin could be a potentially therapeutic anti-cancer agent, as it significantly inhibits prostate cancer growth… and has the potential to prevent the progression of this cancer to its hormone refractory state," the study authors concluded.
Yet prostate cancer is not curcumin's only target. Other cancer investigations have drawn similarly powerful conclusions about this intriguing substance.
A study this past spring at Wayne State University investigated the effect of curcumin on certain gastrointestinal and colon cancers in the lab.(5) Several immunoblot analyses demonstrated that curcumin blocked cell proliferation and induced apoptosis in both gastrointestinal and colon cancer cell lines.
A Chinese study published five years earlier found apoptosis is the result when curcumin is introduced to certain skin, colon, kidney and liver cancer cells, either in cultures or in mouse embryo fibroblasts—large, flat oval cells found in connective tissue and inherent in the formation of fibers.(6)
Other studies using rodents found curcumin is effective in reducing skin inflammation, inhibiting formation of edemas—an abnormal accumulation of cellular fluid, resulting in swelling—and inhibiting skin tumors when the substance is applied topically(7) or orally in concentrations of either 0.2% or 1%.(8)
Curcumin has had similar effects on other types of cancer. When Polish researchers last year assessed the potency of the extract on lymphoid cells—those found in tissues comprising the lymph nodes— apoptosis resulted, although apoptotic symptoms were uniquely different in the various cells tested, the scientists reported.(9)
To determine just how effective curcumin might be as an anticarcinogenic agent, it was compared to other compounds and plant extracts in fighting human oral squamous carcinoma.(10) Cell lines were grown in vitro for 72 hours, then the number of cells were counted to determine proliferation and growth. The researchers found that curcumin was "considerably more potent" compared to plant phenolics genistein and quercetin in inhibiting this type of cancer. Only cisplatin, a platinum-based substance also tested in the study, was found to be more effective.
Still more research focused on the effect of curcumin on the development of pulmonary fibrosis by testing a group of rodents.(11) Scientists in India induced the lung disorder in rats, while giving them dosages of curcumin both 10 days prior and then daily throughout the experiment. Remarkably, curcumin demonstrated its powerful anti-inflammatory and anti-fibrotic effect in each rat studied.
Even breast cancer apparently cannot avoid the power of this extract, which inhibits the growth of breast tumors that result from exposure to environmental estrogenslike chemicals and pesticides, when used in combination with isoflavonoids. Scientists found the curcumin combination inhibited the growth of estrogen receptor-positive cancer cells in a test tube up to 95%.(12)The How's and Why's
What exactly is the mechanism behind curcumin's ability to counteract such a wide array of cancer progression? For several years, medical research focusing on cancer causation has centered on the notion of angiogenesis, the natural blood vessel growth that accompanies metastases. The new blood vessels literally provide nutrition and sustenance to new and growing tumors throughout the body. That may be one basis, medical researchers contend, for curcumin's efficacy. In 1998, Harvard researchers tested the substance for its ability to inhibit the growth of endothelial cells; those which line the interior of blood vessels, as well as the growth of new blood vessels in the corneas of mice.
"Curcumin effectively inhibited endothelial cell proliferation in a dose-dependent manner," they wrote. "Curcumin and its derivatives [also] demonstrated significant inhibition of …corneal neovascularization in the mouse…These results indicate that curcumin had direct antiangiogenic activity in vitro and in vivo. The activity of curcumin in inhibiting carcinogenesis in diverse organs such as the skin and colon may be mediated in part through angiogenesis inhibition."(13)
Other studies, such as one by Taiwanese scientists four years ago, examined the molecular mechanisms behind curcumin. They concluded, after studying curcumin's effect on mouse fibroblast cells, that it directly suppresses the expression of nuclear oncogenes, the genetic mutation that launches the process of cancer cell growth, among other things.(14) Other studies have examined the possibility that the mechanisms behind curcumin may lie in its ability to block the activity of specific oxidants, and halt signal transduction pathways between cells during the initial tumor growth process.(15)Tapping Curcumin's Power
There appear to be other promising implications for this seemingly miraculous substance. Research has demonstrated curcumin's neuroprotective benefits following ethanol-induced brain injury by significantly reversing lipid peroxidation and promoting antioxidants in the brain.(16) Scientists have also been successful at suppressing chemically-induced inflammation and hyperplasia—abnormal cell growth that can be a precursor to cancer—in the liver, as demonstrated in rodents.(17)
Some of the newest studies are pointing to curcumin's potential as an inhibitor of viral progression in AIDS.(18) Researchers at the National Cancer Institute analyzed how curcumin inhibits the activity of integrase in the development of the human immunodeficiency virus (HIV). Integrase is the enzyme that inserts HIV's genes into a cell's normal DNA. Based on their observations, the government researchers suggested that new anti-AIDS strategies might have to be developed that point to curcumin as a potent inhibitor of integrase in the development of HIV.
Much earlier studies have examined other causes for curcumin's anti-HIV activity, such as its ability to inhibit the action of protease, another enzyme in the process of viral development.(19)
More recently, scientists have examined how curcumin blocks formation of the Epstein-Barr virus (EPV) associated with HIV. The virus can cause such diseases as infectious mononucleosis and nasopharyngeal carcinoma. In one study,(20) scientists discovered that treating EPV-infected lymphoid cells with curcumin augmented apoptosis, similar to what has been found in cancer research. "A further investigation of this effect may be useful in prevention and therapy of B-cell lymphoma in immunodeficient patients," the researchers wrote.
Doctors have even found that curcumin, among other common spices, can prevent bacteria such as E. coli from being destroyed by irradiation.(21) The findings, reached in a study from India, carry implications that curcumin and other spice extracts could be used to protect healthy tissue in people undergoing radiation therapy. It is believed that the spices used in the study—red chili powder, black pepper and turmeric—provided their protective effect by blocking the bacteria's DNA from radiation exposure. The researchers added that there is no cause for concern because irradiation doses typically used to process prepared foods are high enough to kill any E. coli.Review
Study after study over the past five years has demonstrated the benefits of curcumin, a substance found in turmeric. Used as long as 6,000 years ago by Indians and other cultures as a treatment for a range of ailments, medical experts more recently are beginning to discover its untapped potential.
Medical science has found signs of curcumin's abilities to fight tumor formation and growth in cancer by inducing the programmed cell death known as apoptosis and inhibiting metastases. Curcumin has also been implicated as an anti-inflammatory, a scavenger of free radicals, a treatment for certain eye diseases and conditions like cataracts, an effective therapy against ethanol-induced brain damage, hyperplasia and as an inhibitor of the human immunodeficiency virus. Before much longer, it may be plausible to think curcumin could spark a medical revolution.Curcumin and Cancer
Cancer cells are everything we would like healthy cells to be. They quickly adapt to toxic environments, they readily alter themselves to assure their continued survival, and they are immortal. All of these factors make cancer an extremely difficult disease to treat.
Chemotherapy drugs have a high rate of failure. That's because these drugs usually kill only specific types of cancer cells within a tumor, or the cancer cells mutate and become resistant to the chemotherapy.
An example of how cancer cells mutate to ensure their survival can be seen in the recently approved "miracle" drug Gleevec (STI-571). This drug produced striking benefits in the treatment of chronic myeloid leukemia and was quickly approved by the FDA. In a recent clinical trial, however, many patients relapsed as their cancer cells grew resistant. Doctors found that a protein in the cellular DNA targeted by STI-571 altered its shape, thus rendering the drug useless in killing these mutant cancer cells. The company that makes STI-571 is already developing strategies to overcome this resistance, but this case of a new drug quickly losing its effectiveness is an illustration of how easily cancer cells will mutate to avoid total eradication.
Oncologists are increasingly using combination chemotherapy regimens that consist of several cytotoxic drugs that work by different mechanisms of action. The objective is to obliterate as many different types of cancer cells within the tumor, or interfere with as many cancer cell survival factors as possible. Despite the use of these potent multi-drug cocktails, 552,000 Americans died of cancer last year.Curcumin's Potential Anti-Cancer Benefits
Curcumin may be effective in helping to suppress the escape mechanisms cancer cells use to avoid eradication by conventional therapies. Curcumin has been shown to inhibit cancer cell propagation via the following mechanisms:
- Inhibiting the epidermal growth factor receptor site (EGFR), in a dose dependent response. Two thirds of all cancers over-express this receptor as a primary means for hyper-proliferation.
- Inhibiting induction of the basic fibroblast growth factor (bFGF). This is responsible for angiogenesis of endothelial cells. Curcumin's effect here again was a dose dependent response.
- Inhibiting expression of cyclooxygenase-2 (COX-2), the enzyme involved in the production of PGE2, a tumor promoting prostaglandin.
- Inhibiting a transcription factor in cancer cells known as nuclear factor kappa beta (NF-kB). Many cancers over-express NF-KB and use this as a growth vehicle to escape cell regulatory control.
- Increasing expression of nuclear p53 protein in human basal cell carcinomas, human hepatomas and leukemia cell lines. This increases apoptosis (cell death) in these cancers.
- Inhibiting induction of hepatocyte growth factor (HGF). Over-expression is involved in hepatcellular carcinoma.
Based on the multiple favorable mechanisms listed above, higher-dose curcumin would appear to be a useful supplement for cancer patients to take.
As far as curcumin being taken at the same time as chemotherapy drugs, there are contradictions in the scientific literature. Some studies indicate significant benefit, whereas other studies hint at reduced benefit or even potential toxicity.
Chemotherapy drugs are highly toxic in and of themselves. Whether high-dose curcumin is beneficial or detrimental depends on the type and dose of the chemotherapeutic drug used, the kind of cancer cell being attacked, and the dose of the curcumin. Until more definitive information is published, we prefer to err on the side of caution and recommend that chemotherapy patients wait four weeks after their last dose of chemo before taking high-doses of curcumin.
Life Extension believes the multiple mechanisms of curcumin's actions against cancer cells warrants aggressive further investigation. We will keep members fully informed of our findings, but at this time, we have to take a cautious stance and officially state that high-dose curcumin should not be taken with anti-cancer drugs.
Cancer patients are faced with many difficult treatment choices. With the exponential increase of new scientific information, conflicts will inevitably occur. Life Extension remains at the forefront in evaluating new scientific data to help members make informed choices.Curcumin Dosing
As far as prevention is concerned, the evidence is substantial that curcumin may be effective in protecting against cancer and a host of other diseases.
For disease prevention purposes, healthy people typically take 900 to 1800 mg of curcumin (with piperine added to enhance assimilation into the bloodstream) a day. Cancer patients often take two to three times this much curcumin-piperine for a six to twelve month period and then taper off the dose.References
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