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Life Extension Magazine

LE Magazine September 2001

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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

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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.

Arbiser JL, et al. Curcumin is an in vivo inhibitor of angiogenesis. Mol Med 1998 Jun;4(6):376-83.

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.


Article References

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4. Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate 2001 Jun 1;47(4): 293-303.

5. Moragoda L, Jaszewski R, Majumdar AP. Curcumin induced modulation of cell cycle and apoptosis in gastric and colon cancer cells. Anticancer Res 2001 Mar-Apr;21(2A):873-8.

6. Jiang MC, Yang-Yen HF, Yen JJ, Lin JK. Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines. Nutr Cancer 1996;26(1):111-20.

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8. Limtrakul Pn P et al. Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin. BMC Cancer 2001;1(1):1

9. Bielak-Zmijewska A et al. Effect of curcumin on the apoptosis of rodent and human nonproliferating and proliferating lymphoid cells. Nutr Cancer 2000;38(1):131-8.

10.Elattar TM, Virji AS. The inhibitory effect of curcumin, genistein, quercetin and cisplatin on the growth of oral cancer cells in vitro. Anticancer Res 2000 May-Jun;20(3a):1733-8.

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13.Arbiser JL et al. Curcumin is an in vivo inhibitor of angiogenesis. Mol Med 1998 Jun;4(6):376-83.

14.Lin JK, Chen YC, Huang YT, Lin-Shiau SY. Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin. J Cell Biochem Suppl 1997;28-29:39-48.

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16.Rajakrishnan V et al. Neuroprotective role of curcumin from curcuma longa on ethanol-induced brain damage. Phytother Res 1999 Nov;13(7):571-4.

17.Chuang SE, Cheng AL, Lin JK, Kuo ML. Inhibition by curcumin of diethylnitrosamine-induced hepatic hyperplasia, inflammation, cellular gene products and cell-cycle-related proteins in rats. Food Chem Toxicol 2000 Nov;38(11):991-5.

18.Mazumder A et al. Inhibition of human immunodeficiency virus type-1 integrase by curcumin. Biochem Pharmacol 1995 Apr 18;49(8):1165-70.

19.Sui Z, Salto R, Li J, Craik C, Ortiz de Montellano PR. Inhibition of the HIV-1 and HIV-2 proteases by curcumin and curcumin boron complexes. Bioorg Med Chem 1993 Dec;1(6):415-22.

20.Ranjan D et al. Enhanced apoptosis mediates inhibition of EBV-transformed lymphoblastoid cell line proliferation by curcumin. J Surg Res 1999 Nov;87(1):1-5.

21.Sharma A, Gautam S, Jadhav SS. Spice extracts as dose-modifying factors in radiation inactivation of bacteria. J Agric Food Chem 2000 Apr;48(4): 1340-4.



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