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Life Extension Magazine

Life Extension Magazine November 2011
Report

The Inflammatory Factor Underlying Most Cancers

By David Hoffnung
Reducing the Risks of High Cortisol

Implicated in the onset of 95% of all cancers is a common but under-recognized molecule most people have never heard of: nuclear factor-kappaB or NF-kB.1-3 Emerging research is validating the danger it poses to maturing individuals.

For example, a landmark study4 published late last year confirmed, for the first time, NF-kB’s central role in the onset of malignant breast cancer.

A team of researchers found that breast cancer cells require a specific inflammatory cascade in order to proliferate and metastasize.

As one of the proteins that activates genes involved in inflammation, NF-kB is the master regulator of this pathologic cancer-causing process.

Fortunately, there exists a broad array of nutrients many Life Extension® members already take that have been shown to neutralize and even reverse the cancer-causing inflammatory cascade mediated by NF-kB.

In this article, a comprehensive survey of NF-kB-inhibiting compounds is detailed. You will learn how NF-kB triggers the growth and development of many kinds of tumors, operating as the master switch for cells “pre-loaded” with cancer-causing genes. You’ll also discover compelling evidence about low-cost interventions that suppress NF-kB, switch off lethal cancer genes, and disrupt the inflammatory cascade cancer cells need in order to spread.

Milk Thistle
Milk Thistle

Since its discovery in 1986, NF-kB has been known to be closely associated with development of cancer.5 Today we know that most, if not all cancers have abnormally high levels of active NF-kB, which keeps them in a state of sustained inflammation.6 Conversely, certain so-called oncogenes (abnormal genes that can initiate cancer development) act in part by activating NF-kB.7 Together these facts conspire to produce a steady stream of inflammatory and cancer-promoting cytokines within a growing tumor.8

The production of these cell signaling molecules makes it much more likely that a given cancer-prone cell will go on to form a malignant tumor. It can also mean that a given tumor is much more resistant to radiation and chemotherapy, since NF-kB generally promotes cancer cell survival.9

The NF-kB-Cancer Blockade

NF-kB triggers the cascade of events that link inflammation with cancer development. Once that process has been initiated, NF-kB continues to fan the flames, contributing to cancer cells’ invasiveness, ability to stimulate a fresh blood supply, and ability to spread by metastasis throughout the body.

But our knowledge about the damage done by NF-kB can be turned to good. Almost as soon as it was discovered, forward-thinking researchers recognized that if they could block activation of NF-kB, they might break an essential link in cancer development.

We’ve known for nearly 12 years, for example, that we could reduce inflammation in colon cancer cells by treatment with the spice curcumin, a well-known inhibiter of NF-kB activation.10 Blocking NF-kB activation can also sensitize human prostate cancer cells to apoptosis—the programmed cell death that keeps cancers under control.11 And natural molecules that inhibit NF-kB can limit inflammatory changes in the pancreas caused by alcohol.12

The potential for blocking NF-kB offers hope in the context of the deadly HER-2 breast cancer gene. HER-2 cancers are normally highly treatment-resistant and carry a poor prognosis.6 Blocking NF-kB can make the breast cancer cells more amenable to chemotherapy.8,13

Not surprisingly, Big Pharma is intensely interested in discovering new (and profitable) drugs that block NF-kB.14 But nature has provided us with a substantial number of substances that block or inhibit the pro-inflammatory, pro-cancer effects of renegade NF-kB—and they are readily available, affordable, and safe. Let’s look at a sampling.

Nutrients to Quell NF-kB’s Inflammatory, Pro-Cancer Effects

By some estimates, anywhere from 67% to 90% of human cancers could be prevented by modifications to lifestyle, specifically to diet.14,15 Suppression of NF-kB by phytochemicals present in fruits, vegetables, and many spices has in fact been said to provide the molecular basis for their ability to prevent cancer.16,17

Nutrients to Quell NF-kB’s Inflammatory, Pro-Cancer Effects

The following nutraceutical agents can bring us closer to successful chemoprevention through their ability to oppose NF-kB’s pro-inflammatory, pro-cancer effects. Unlike single-targeted drugs, most nutraceuticals are multitargeted. That gives them astonishing efficiency and can augment their effectiveness, especially when acting to interrupt complex signaling pathways like those involved with NF-kB.18

Antioxidants

Oxidative damage to DNA, proteins, and other vital structures is a major factor in the initiation, promotion, and spread of cancers. That makes antioxidants important agents in the fight to prevent cancer.19 But many antioxidants can also block NF-kB, adding a valuable degree of specificity to their effects. They do this via a number of closely related but distinctive mechanisms.14

One important way of blocking NF-kB activity is to prevent it from becoming activated by moving into the cell nucleus. That denies NF-kB access to the pro-inflammatory genes that it regulates, thereby preventing the inflammatory response before it starts. Cells with greater levels of internal antioxidant defenses generally have less NF-kB activation. Increasing those defenses is correlated with reduced NF-kB expression in cell nuclei.20,21

A large number of antioxidants are under review for specific NF-kB-blocking activity. These include vitamins C and E, carotenoids, the so-called thiol antioxidants (glutathione, thioredoxin, and lipoic acid), flavonoids and polyphenols, selenium, zinc, and others.14,19,22,23 The flavonoid luteolin, for example, can sensitize cancer cells to chemotherapy agents by suppressing a variety of cell-survival pathways, including NF-kB.24 And zinc, an essential trace element, inhibits NF-kB indirectly by inducing a separate regulatory protein called A-20.25

Milk thistle extracts enhance prostate cancer cell death through apoptosis by reducing levels of NF-kB in the cell nucleus.26,27 The tomato carotenoid pigment lycopene prevents NF-kB activation in prostate cancer by a different mechanism.28 A form of vitamin E called gamma-tocotrienol downregulates NF-kB in pancreatic tumor cells.29 Even certain coffee components, the antioxidant molecules called diterpenes, suppress NF-kB activation.30 And a host of antioxidant compounds derived from black pepper reduce NF-kB activation.31 Finally, the tomato polyphenol lycopene reduces NF-kB activation in a variety of cancer cell types.28

What You Need to Know: The Inflammatory Factor Underlying Most Cancers
  • A breakthrough study 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.

Clearly, the list of antioxidant nutrients with NF-kB-suppressing effects is growing rapidly. A good general rule for the present is to make certain that you are including an adequate supply of potent, high-quality antioxidants as part of your health regimen. Let’s now turn to some specific nutrients that have additional NF-kB-blocking effects that can optimize your cancer protection.

Curcumin

The Inflammatory Factor Underlying Most Cancers

Curcumin is an extraordinary molecule extracted from the spice we know as turmeric. It is among the most potent of the natural inhibitors of NF-kB, and as such has been intensely studied for its anticancer potential.32

Curcumin is beneficial at all three major stages of carcinogenesis: initiation, progression, and promotion.33 Most of that benefit has been linked to its inhibition of NF-kB and subsequent inhibition of pro-inflammatory signaling.33 NF-kB inhibition is also credited with curcumin’s ability to inhibit cancer cell proliferation, invasion, new blood vessel formation, and metastasis.34 Another major consequence of NF-kB inhibition by curcumin is to allow the natural course of apoptosis to take place in cancer cells, triggering them to die off rather than multiply and spread.35

Curcumin is showing promise in treating or preventing some of mankind’s most common, and most dangerous, malignancies. These include chronic lymphocytic leukemias, lymphomas, pancreatic cancers, bladder cancer, colon cancer, and cancer of the bile ducts.36-44 And curcumin can help to suppress the cancer-provoking inflammation generated by obesity, one of today’s most pressing health problems.45

NF-kB and the Cancer Switch

NF-kB is scientifically known as a “transcription factor.”92 It regulates how and when the information in certain human genes becomes translated into new protein molecules.

Key among those genes are those that promote inflammatory responses, many of which also promote cell growth, survival, and transformation into cancer.6,22 In fact, in the early 2000s it became clear that NF-kB was the “missing link” between inflammation and cancer.93 Of course, that’s not its only role.

In healthy people, NF-kB serves a vital function just by remaining inactive. That helps to keep the powerful cellular machinery of inflammation running just at idle. When a threat arises, however, NF-kB becomes activated and goes to work within the nuclei of cells (hence the term “nuclear factor”).7

A cell’s nucleus is where all the genetic information is stored in the form of DNA in our chromosomes. Under normal circumstances, NF-kB “lives” not in the nucleus, but in the cell’s cytoplasm, the main body of the cell.7 When an infection or other foreign invader threatens, NF-kB moves from the cell’s cytoplasm into its nucleus.7 Once inside the nucleus, NF-kB binds to specific portions of the chromosome, where it activates transcription of a gene into its protein product.

Many genes that come under the control of NF-kB are pro-inflammatory genes, that is, their products are inflammatory cytokines such as interleukins, tumor necrosis factor, and others. Once the inflammatory stimulus goes away, NF-kB normally disengages from the chromosome and returns to the cytoplasm, and the inflammatory gene stops producing its cytokines. In other words, under normal circumstances, inflammation dies away when it is no longer beneficial.94

But that’s only under normal circumstances, and cancer is anything but normal.

Garlic Extracts

Garlic, like turmeric, has a lengthy history of use in traditional medical systems. When garlic extracts are allowed to age, they stabilize and retain strong antioxidant powers that indirectly down-regulate NF-kB.46 Individual components from such garlic extracts include diallyl sulfide, diallyl disulfide, and thiacremonone, all of which demonstrate direct NF-kB-inhibitory activities.17,47,48

NF-kB inhibition by garlic extracts is showing promise in preventing growth and spread of many tumor types, including colon cancer, malignant neuroblastoma, and melanoma.47-51 Garlic extracts also powerfully induce cancer cell death by apoptosis.49,51