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Life Extension Magazine

Life Extension Magazine November 2011
Report

The Inflammatory Factor Underlying Most Cancers

By David Hoffnung

Ginger

Ginger is a spice from southern Asia, that has many health-giving specific components.52 Gingerol is the chief of these; it is a phenolic compound with antioxidant, anti-inflammatory, and anti-tumor properties.53 Gingerol suppresses inflammation by blocking the movement of NF-kB into the nucleus, with the resulting down-regulation of such inflammatory cytokines as TNF-alpha, as well as inducible nitric oxide synthase (iNOS).52,53 Another major ginger compound, zerumbone, suppresses NF-kB activation induced by a host of common carcinogens, blocking metastasis and invasion while increasing apoptosis.54

Ginger extracts have been used to reduce the viability of gastric cancer cells, ovarian cancers, cancers of the breast, liver, colon, and lung, as well as UV light-induced skin cancers.55-60

Current NF-kB Research
Current NF-kB Research

Here’s what we know in 2011 about the relationship between NF-kB and cancer, courtesy of Dr. Sahdeo Prasad of the Cytokine Research Laboratory at the MD Anderson Cancer Center in Houston:5

NF-kB becomes activated in response to a host of factors that account for as much as 95% of all cancers. These triggers include tobacco, stress, dietary components, obesity, alcohol, infections, radiation, and environmental toxins.1-3

NF-kB activation has been linked with the transformation of normal cells into cancer cells (thus NF-kB can be thought of as promoting cancer development).1,95

NF-kB is active at a higher rate in cancer cells than in healthy cells. A developing cancer also increases the amount of active NF-kB.6,13

NF-kB has been linked to the survival of dangerous cancer stem cells, the early “parent” cells of many cancers that are now known to exist in otherwise normal tissues. Cancer stem cells can “self-renew” more successfully than healthy cells.

NF-kB stimulates production of gene products that keep cancer cells from dying naturally through the process of programmed cell death, or apoptosis.96

NF-kB also increases production of gene products associated with proliferation, the rapid and repeated cell divisions that give cancers their aggressive growth characteristics.97

NF-kB controls expression of gene products linked with invasion, new blood vessel growth (angiogenesis), and metastatic spread of tumors.96,98-100

Many carcinogens activate NF-kB, but most effective cancer-preventing (chemopreventive) compounds suppress NF-kB activation.1,15,101

Prasad notes that these observations highlight just how intertwined NF-kB is with cancer growth and metastasis.5 Others have gone on to point out that, though a powerful nemesis, NF-kB also offers myriad opportunities to intervene powerfully and block cancers in their tracks.8,13 As we continue to clarify the close relationship between chronic inflammation and cancer, more and more such opportunities are becoming evident.93

Green Tea

Green tea extracts are widely known for their benefits in preventing many common chronic diseases. Their chief constituents, the catechin family of polyphenols, are powerful antioxidants that are given credit for most of tea’s beneficial effects.61,62 Catechins act at many different targets.18,63,64 Inhibition of NF-kB by green tea catechins has recently been found to be a major mechanism by which they block each stage of carcinogenesis.63-65

NF-kB inhibition by green tea extracts rich in epigallocatechin gallate (EGCG) has been of particular interest.866 EGCG has been shown to produce apoptosis in experimental prostate cancer, inhibit growth of squamous cell carcinomas of the head and neck, inhibit production and limit invasion of experimentally induced breast cancers, reduce the incidence of carcinogen-induced lung cancers, and sensitize melanoma cells to growth inhibition by other agents.67-71

Isoflavones

Omega-3 Fatty Acids

Isoflavones and isoflavonoids are molecules found in many plants, particularly the bean family. Plants use them as disease-fighting compounds, and also as stimulants for the symbiotic bacteria that help them use nitrogen to build proteins. Isoflavones from soybeans have many beneficial and protective effects in humans as well. The low rate of hormone-related cancers (e.g., breast and prostate cancers) in Asian countries is partially attributed to the high consumption of soy isoflavones in most traditional Asian diets.72,73

Soy isoflavones like genistein are powerful modulators of NF-kB.73 Genistein acts both by preventing NF-kB’s movement into the nucleus to activate inflammatory genes and also by preventing earlier molecular events that would lead to its activation.74 Genistein promotes cancer cell death by apoptosis as a result of down-regulation of NF-kB.74

Isoflavone blockade of NF-kB effects contributes to prevention and modulation of colon75 and lung cancers.76 Isoflavone treatment also makes certain cancer cells increasingly susceptible to radiation and chemotherapy effects, largely because decreased NF-kB activity impairs the cancer cells’ survival signaling pathways.73,77,78

Omega-3 Fatty Acids

Diets rich in omega-3 fatty acids from fish are associated with reduced risk of several types of cancer and other chronic conditions.79,80 The omega-3s are known to be powerful anti-inflammatory agents through their effects on the important inflammatory enzymes like COX-2 and 5-LOX.81 But recent research is also showing that omega-3s can inhibit NF-kB activation by multiple mechanisms, giving them still more powerful control over the inflammation that can lead to cancers.

Omega-3s are now associated with NF-kB-related reduction in inflammation-mediated growth of pancreatic, breast, prostate, colon, and skin cancer cells.82-90 In the case of pancreatic cancer, the omega-3 EPA preserved the integrity of the natural inhibitor of NF-kB.82 Omega-3s used in combination with conventional chemotherapy act synergistically to kill tumor cells, largely through NF-kB inhibition that promotes apoptosis.89,91

Summary

A breakthrough study published late last year revealed that inflammation is necessary in order for breast cancer cells to proliferate and metastasize. The master control complex called nuclear factor-kappaB or NF-kB triggers and regulates this inflammatory cascade, which has been implicated in the onset and development of 95% of all cancers.

NF-kB stimulates genes to produce inflammatory cytokines and other signaling molecules that promote cancer growth and development. Inhibition of NF-kB is a powerful target for cancer prevention and has been shown to reduce cancer-stimulative events at every level of carcinogenesis (cancer development). A broad array of natural dietary interventions powerfully inhibits pathologic NF-kB activity, comprising a critical strategy in the fight against cancer. Scores of new studies detail the effects of NF-kB inhibition on cancer prevention. The low rates of cancers in countries with high dietary intake of natural NF-kB inhibitors points strongly to the value of such agents as functional foods and as nutraceuticals.

In addition to the many natural products outlined here, there’s now strong evidence that vitamin D, Withania somnifera (ashwagandha), and pomegranate extracts have similar NF-kB-blocking capabilities.102-104

The good news for Life Extension members is that they have been using potent NF-kB-inhibiting nutrients for many decades.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at
1-866-864-3027.

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