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Curcumin and Other Anti-inflammatory Herbs in Cancer Prevention and Adjunctive Management

Evidence suggests that 70-90% of colon cancer cases are caused by faulty nutrition and other factors associated with lifestyle.Coloncancer continues to be the second leading cause of cancer death in North America with about 140,000 new cases diagnosed each year in theUnited States.

Despite recent advances in medicine, mortality remains unacceptably high. It is noteworthy however, that periodic colonoscopy assessment after age 50 years of age (or earlier in individuals with a strong family history) is associated with a 15-33% reduction in risk of colon cancer death. Thus, early detection of colon cancer via colonoscopy screening in high-risk individuals and those over 50 years of age is a prudent primary prevention step.new_ha

With respect to preventing colon cancer development dietary modifications linked to reduced colon cancer incidence include consuming a low animal fat diet with minimum intake of trans and hydrogenated fats, consuming more fiber, fruits and vegetables, especially cruciferous vegetables, as well as allium-containing foods (garlic and onions) and omega-3 fats, minimizing alcohol consumption and attaining optimal levels of folic acid, calcium, vitamin D, selenium, antioxidants and several other micronutrients.

It is also best to minimize intake of barbequed foods (the charring of such foods results in the formation of highly carcinogenic chemical compounds), and sodium nitrite found in many processed foods. 

Cell Membrane Receptors and Cancer

In recent years cancer researchers have discovered that an important part of the puzzle in colon cancer development lies in the expression of certain cell membrane receptors and their stimulation by various chemical agents (ligands). Stimulation of various cell membrane receptors by specific ligands produce profound effects on cellular proliferation, cell growth, cell differentiation and apoptosis (programmed cell death). As an example, the binding of vitamin D to the vitamin D receptor on the cell membrane, triggers a series of reactions (known as signal transduction) that ultimately promotes the induction of intracellular messengers, which slow the rate of cell division, and promotes cell maturation; two outcomes linked to reduction of cancer development.

On the other hand the over-expression of Epidermal Growth Factor Receptors (EGFR) and other members of the tyrosine kinase family are frequently indicated in epithelial cancers, including colon cancer.

The epidermal growth factor (EGF) family of receptor tyrosine kinases consists of four receptors, EGF-R (ErbB1), ErbB2 (Neu), ErbB3, and ErbB4.

In response to these discoveries pharmaceutical companies have produced a number of drugs that inhibit the activation of specific receptors of the EGFR series (EGFR inhibitor drugs). However, in general these drugs have had limited success because cancer cells usually possess more than one type of EGFR receptor. As such, researchers conclude that what is needed to help prevent colon cancer, as well to help treat colon cancer, is a broad-spectrum EGFR receptor inhibitor that inhibits signal transduction for all EGFR cell membrane receptors. (pan-erb signal transduction inhibitors). To this end there is a naturally-occurring pan-erb signal transduction inhibitor that is showing promise in experimental and animal studies, known as EGFR Related Protein. This protein occurs naturally and thus, its use as targeted therapeutic agent is unlikely to produce toxic side effects. 

Curcumin Is A Natural Pan-erb Signal Transduction Inhibitor In Cancer Prevention

With respect to natural medicine, it is well documented that curcumin, the active ingredient in the spice turmeric, also acts as a powerful inhibitor of EGFR receptors. Experimental studies, animal studies and a recent Phase I clinical trial, have shown that curcumin inhibits the growth of colon cancer cells and reduces tumor incidence in high risk human subjects. Curcumin inhibits the EGFR receptor, which in turn inhibits the propagation of metabolic reactions (e.g. decreased synthesis of the tumor promoting messenger NF-kB) leading to inhibition of cell replication of cancer cells and preneoplastic cells.

Curcumin also exerts anti-inflammatory effects on cells by inhibiting synthesis of pro-inflammatory prostaglandins. Inhibiting pro-inflammatory prostaglandins has also been shown to reduce cancer risk of colon cancer as demonstrated by studies linking the effects of aspirin and other non-steroidal anti-inflammatory drugs to reduced incidence of colon cancer. However, unlike aspirin, curcumin does not cause gastrointestinal erosion leading to ulceration and bleeding disorders.

As such, daily supplementation with curcumin may be viewed as part of a chemoprevention strategy to help reduce risk of colon cancer development.

Prostaglandin series-2 and it is metabolites have been shown to contribute to the cancer processes through one or more of several mechanisms including increased proliferation, apoptosis, enhanced carcinogen metabolism or modulation of the immune system

Along with curcumin, other anti-inflammatory herbs that block the activity of cyclooxygenase and/or lipoxygenase (6 and/or 12 lipoxygenase), inhibiting synthesis of prostaglandin series-2 and its metabolites (related eicosanoids of the PGE-2 series) have also shown promise as agents to reduce risk of cancer, including colon cancer. The herbs of most importance in my view include white willow extract, ginger and boswellia.

Many holistic health practitioners have recognized the value of these herbs as non-toxic, anti-inflammatory supplements that are useful in the management of inflammatory musculoskeletal conditions (e.g. arthritis, tendonitis, fascitis, bursitis). However, like curcumin, each of these herbs also demonstrates anti-cancer properties as well.

The main ingredients in ginger that have an anti-inflammatory effect, as well as antitumor and antiproliferative properties against tumor cells, are 6-gingerol and 6-paradol, which are found in the oleoresin fraction in ginger. Other constituents of ginger, 8-paradol and 8-shogaol, demonstrate a significant inhibitory effect on the cyclooxygenase enzyme system, which in turn, reduces the synthesis of prostaglandin series-2 metabolites.  As such, ginger supplements should be standardized to contain 5% gingerols.

Gummy exudates of the herb boswellia have been traditionally used as anti-arthritic and anti-cancer mediations. Boswellic acid and its acetates isolated from these gummy exudates were found to be inhibitors of topoisomerases and to be non-redox, non-competitive specific inhibitors of 5-lipoxygenase (5-LOX).

All of these properties are key factors in preventing and controlling cancer. Experimental evidence has shown that boswellic acid acetates isolated from Boswellia carterri Birdw inhibit cell growth and induce apoptosis (programmed cell death) in prostate cancer cells by inhibition of 5-lipoxygenase. Other studies have shown that boswellic constituents exhibited potent cytotoxic activities against three types of human neuroblastoma cells.

White willow bark contains salicin.  The role of salicylates in inflammation and pain management is well documented in medicine.  Salicin is a potent inhibitor of cyclooxygenase and thus reduces synthesis of prostaglanding series-2 and its metabolites.

Ingestion of acetylsalicylic acid (aspirin) is highly associated with reduced risk of colon cancer in human epidemiological studies.  However, unlike aspirin, salicylic acid from white willow bark does not cause intestinal erosion or bleeding and does not impair platelet coagulation to an appreciable degree.

As such, white willow bark extract has a much higher safety profile than synthetic aspirin.  To be effective white willow bark extract should be standardized to contain 15% salicin. 

Summary

A strong body of evidence indicates that an important aspect of cancer prevention involves containment of prostaglandin series-2 synthesis and inhibition of cell membrane receptors associated with the receptor tyrosine kinase family (EGFR, ErB-2, ErB-3 and ErB-4). Curcumin, derived from the spice turmeric, has shown significant anti-tumor properties against colon cancer. Curcumin has been shown to inhibit the receptor tyrosine kinase family and decreases synthesis of prostaglandin series-2.

The anti-inflammatory herbs ginger, boswellia and white willow bark extract have also been shown to inhibit prostaglandin series-2 synthesis, as well as other pro-inflammatory mediators, and experimental evidence suggests that their active constituents possess important anti-tumor properties.

As such, health practitioners may wish to encourage their patients to ingest a herbal combination supplement product each day containing curcumin, ginger, white willow bark extract and boswellia, as an additional part of a wellness and cancer prevention program. This may have important applications especially in regards to colon cancer, the second leading cause of cancer death.

A suggested combination formula would include taking two capsules per day of the following supplement, to derive sufficient dosages of the active ingredients in these herbs for chemoprevention purposes. Slightly higher dosages would be required to manage moderate to severe inflammatory conditions. I now take this combination myself as part of my cancer prevention campaign.

Curcumin 200 mg
Boswellia (std to 70% boswellic acids) 200 mg
White Willow Extract (std to 15% salicin content) 33 mg
Ginger Root Extract (std to 5% gingerols content) 50 mg





References:

  • Reddy S, Rishi A.K., Xu H et al. Mechanisms of curcumin-and EGF-receptor related protein (ERRP) – dependent growth inhibition on colon cancer cells. Am J Clin Nutr, 55; 2: 185-194. 2006
  • Ciardiello, F, Caputo R,  Bianco, R.  Antitumor Effect and Potentiation of Cytotoxic Drugs Activity in Human Cancer Cells by ZD-1839 (Iressa), an Epidermal Growth Factor Receptor-selective Tyrosine Kinase Inhibitor.  Clinical Cancer Research; 6: 2053-2063, May 2000
  • Ciardiello F and Tortora G. Interactions between the epidermal growth factor receptor and type I protein kinase A: biological significance and therapeutic implications. Clinical Cancer Research, 4,; 4: 821-828: 1998
  • Al-Achi. Anti-inflammatory Herbs.U.S.Pharmacist. 29:03 (Posted 03/15/2004)
  • McCarty M.F. Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy. Integrative Cancer Therapies 3; 4:349-380. 2004
  • Wells, A. EGF receptor. Int. J. Biochem. Cell Biol., 31: 637-643. 1999.

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