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.

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Gorre, M.E. et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science Jun 21, 2001.

Hanahan D, et al. Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 2000 Apr;105(8):1045-7.

Jee SH, et al. Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. J Invest Dermatol 1998 Oct;111(4):656-61.

Korutla L, et al. Inhibition of ligand-induced activation of epidermal growth factor receptor tyrosine phosphorylation by curcumin. Carcinogenesis 1995 Aug;16(8):1741-5.

Seol DW, et al. Transcritional activation of the hepatocyte growth factor receptor (c-met) gene by its ligand (hepatocyte growth factor) is mediated through AP-1. Oncogene 2000 Feb 24;19(9):1132-7.

Shoba G,,et al. Influence of piperine on the pharmacokinetics of cuccumin in animals and human volunteers. Planta Med 1998 May;64(4):353-6.

Zhang F, et al. Curcumin inhibits cyclooxygenase-2 transcription in bile acid phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis 1999 Mar;20(3):445-51.

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