How Curcumin Protects Against Cancer - Life Extension

As mainstream oncology misguidedly focuses on toxic, single-agent treatments, a wealth of compelling data puts curcumin at the forefront of multimodal cancer prevention.

Life Extension Magazine®
Issue: Mar 2011

According to the American Cancer Society,1 one out of every three women in the United States risks developing some form of cancer over the course of their lives. For men, that number rises to one in two. Since cancer is an age-related disease, the risk of diagnosis increases the longer one lives, making it the second leading cause of death in this country.2,3

These data underscore a stark reality. When it comes to cancer prevention, the medical establishment and drug company profiteers remain grossly negligent in protecting the public. The result is countless avoidable cancer deaths each year. There is an urgent need to provide aging individuals with validated interventions to target cancer’s multiple causative factors before they take hold.

Among the most compelling and underrecognized of these is curcumin. In contrast to mainstream oncology’s focus on single-agent toxic treatments, curcumin has emerged as a potent multimodal cancer-preventing agent, with 240 published studies appearing in the global scientific literature in the past year alone.

In this article, you will learn of the multiple factors involved in carcinogenesis (cancer development). You will discover up-to-date research demonstrating curcumin’s power to disrupt specific molecular mechanisms that lead to cancer—and to even treat the disease in many cases.

System-Wide, Safe, Multimodal Defense

Curcumin is derived from the Indian spice turmeric and possesses several active components, all of which contribute to its anti-inflammatory and chemopreventive power.4-6 In fact, curcumin targets ten causative factors involved in cancer development.

Disrupting any one of these factors gives you a good chance of preventing cancer; disrupting several provides even greater protection, including the prevention of DNA damage.7

By blocking the inflammatory master molecule nuclear factor-kappaB (or NF-kB), curcumin blunts cancer-causing inflammation, slashing levels of inflammatory cytokines throughout the body.8,9 Curcumin also interferes with production of dangerous advanced glycation end products that trigger inflammation which can lead to cancerous mutation.10

Curcumin alters cellular signaling to enhance healthy control over cellular replication, which tightly regulates the cellular reproductive cycle, helping to stop uncontrolled proliferation of new tissue in tumors.11 It promotes apoptosis in rapidly reproducing cancer cells without affecting healthy tissue11-13 and reins in tumor growth by making tumors more vulnerable to pharmacologic cell-killing treatments.11,14

In addition, curcumin regulates tumor suppressor pathways and triggers mitochondrial-mediated death in tumor tissue, thereby increasing the death of cancer cells.11,15

Finally, curcumin interferes with tumor invasiveness and blocks molecules that would otherwise open pathways to penetration of tissue.2 It also helps to starve tumors of their vital blood supply and it can oppose many of the processes that permit metastases to spread.8,16,17 These multi-targeted actions are central to curcumin’s capacity to block multiple forms of cancer before they manifest.

Combating Deadly Cancers in Women

Breast cancers vary widely in their responsiveness to standard treatment. Cancers that depend on the hormone estrogen for survival are more effectively treated with conventional methods. Those that lack receptors for female hormones are far more resistant to treatment. This is where curcumin’s value truly lies, because it has the ability to induce apoptosis (programmed cell death) in a variety of hormone-negative cancers.18-20 Remarkably, curcumin produces virtually no change in healthy breast cells, with very low toxicity even at doses as high as 8,000 mg daily.21

In human cancer patients, curcumin doses as high as 3,600 mg a day have been shown to induce the following favorable anti-cancer effects:

• Paraptosis. A process similar to apoptosis (programmed cell death), curcumin initiates paraptosis only in breast cancer cells, resulting in their rapid destruction.22
• Targeted destruction of cancer-cell mitochondria (leaving mitochondria in healthy cells unaffected).22
• Disruption of the cancer cell cycle. Curcumin can “suspend” cancerous cells in a non-reproductive state within their life cycle, thereby halting their replication.20,23-25
• Cancer cell downregulation. Curcumin blocks a group of molecules vital to the process of metastasis. In animal models, it has been shown to reduce metastatic spread to the lungs via this pathway.17,26,27
• Arrested stem cell development. Curcumin inhibits growth and renewal of so-called cancer stem cells, aberrant cells now believed to be at the root of many cancers, including breast cancer.3,28

Curcumin has also been shown to effectively combat cervical cancer, a leading cause of cancer death in women in developing nations and a common cancer in this country.29 It is caused largely by infection with the human papilloma virus, or HPV. Curcumin’s anti-inflammatory effects break the link that triggers HPV-induced cancer development.29,30

Curcumin further promotes apoptosis of cancer cells within the lining of the uterus and reduces the growth rate of painful but non-malignant uterine leiomyomas (uterine fibroids). 31-34

Collectively, these effects make curcumin attractive both as a primary chemopreventive agent in women at risk for breast cancer and an adjuvant treatment option in those who have already developed the disease.20,21

Prostate Cancer Defense

Prostate cancer is the second leading cause of cancer death in American men.35,44 Fortunately, its long latency period and slow growth rate make it a prime candidate for prevention.36 Curcumin strikes at multiple targets in prostate malignancies, interfering with the spread of cancer cells and regulating inflammatory responses through the master regulator NF-kB.36-38

Like certain breast cancers, prostate cancer is often dependent on sex hormones for its growth. Curcumin reduces expression of sex hormone receptors in the prostate, which speeds androgenic breakdown and impairs cancer cells’ ability to respond to the effects of testosterone.39-42 It also inhibits cancer initiation and promotion43 by blocking metastases from forming in the prostate and regulating enzymes required for tissue invasiveness.44

Combating Gastrointestinal Cancers

Colorectal cancer is the third most common malignancy in adults and the second leading cause of cancer deaths.45,46 Despite aggressive surgical care and chemotherapy, nearly 50% of people with colorectal cancers develop recurrent tumors.47 This may be due in part to the survival of dangerous colon cancer stem cells that resist conventional chemotherapy and act as “seeds” for subsequent cancers.3,48,49

On the other hand, these cancers are excellent candidates for prevention, since they follow a predictable sequence from non-malignant polyps to full-blown cancerous growths, usually requiring a decade to develop.46

Much as with malignancies of the breast, cervix, and prostate, curcumin slows the progression from colon polyp to cancer by damping down the inflammatory cascade triggered by NF-kB and pro-inflammatory cytokines.6 This halts the growth of cancer cells before they can become detectable tumors via a host of interrelated molecular mechanisms.50,51

Curcumin also creates a gastrointestinal environment more favorable to optimal colon health by reducing levels of so-called secondary bile acids, natural secretions that contribute to colon cancer risk.52 That has a direct effect, inhibiting proliferation of cancer cells and further reducing their production.53

Curcumin also suppresses colon cancer when combined with other polyphenols such as resveratrol.46,54 The combination of curcumin with green tea extracts has prevented experimentally induced colon cancer in rats.55

Curcumin also synergizes with standard chemotherapy drugs, helping to boost their efficacy and potentially reduce the dose of toxic chemotherapy products, minimizing needless harm and suffering for cancer patients.45,47-49 Curcumin increases colon cancer cell response to radiation.56

A novel feature of curcumin is its ability to bind to and activate vitamin D receptors in colon cells.57 Vitamin D is known to exert potent anti-cancer properties.

Curcumin is equally powerful at preventing cancers in the stomach. It inhibits growth and proliferation of human gastric cancer cells in the laboratory and is particularly effective in stopping cancers that have become resistant to multiple drug treatment.58-60 Curcumin can prevent gastric cancer cells from progressing through their growth cycle, blocking further tumor growth.60

Infection with the bacterium Helicobacter pylori (H. pylori) is a known cause of gastritis, peptic ulcer, and gastric cancer.61 Curcumin blocks growth of H. pylori and reduces the rate at which stomach cells react by turning cancerous.61,62 This effect is again related to curcumin’s fundamental ability to block activation of inflammatory NF-kB.62

WHAT YOU NEED TO KNOW: MULTIMODAL ANTI-CANCER POWER OF CURCUMIN

Curcumin has emerged as a potent cancer-preventing agent, with 240 published studies appearing in the global scientific literature in the past year alone. Its multimodal effects act to simultaneously counter ten discrete causative factors in cancer development. It intervenes at each stage in the complex sequence of events that enable cancer cells to develop, proliferate, and metastasize. Its multitargeted mechanisms of action have yielded compelling results in combating a remarkably broad array of cancers, including those of the breast, uterus, cervix, prostate, and GI tract. A blossoming body of research reveals curcumin’s promise in countering cancers of the blood, brain, lung, and bladder as well.

Further Preventive Potential

Curcumin’s anti-inflammatory, antioxidant, and gene-regulating powers have been explored in preventing or treating cancers of the blood-forming system (leukemias, lymphomas, and myelomas) as well as those of the brain, lung, and bladder.12,13,63-81 Even aggressive tumors of the head and neck, often following years of smoking, are proving responsive to curcumin treatment.14,82-85 Curcumin is also emerging as a potentially effective intervention for pancreatic cancer—one of cancer’s most lethal and aggressive forms.86-90

Summary

Cancer is the second leading cause of death in the US, and the risk of developing the disease increases significantly as we age.

Curcumin has emerged as a potent cancer-preventing agent, with 240 published studies appearing in the global scientific literature in the past year. Curcumin’s multimodal effects act to simultaneously counter ten discrete causative factors in cancer development.

It intervenes at each stage in the complex sequence of events that must occur in order for a cancer to develop, progress, invade, and ultimately metastasize to healthy tissue.

The multi-targeted mechanisms of curcumin have yielded compelling results in combating a remarkably broad array of cancers, including those of the breast, uterus, cervix, prostate, and GI tract. A burgeoning body of research demonstrates curcumin’s potential to counter cancers of the blood, brain, lung, and bladder as well.

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

Ten Key Causative Factors in Cancer Development More than many other age-related diseases, cancer results from the cumulative effect of years of discrete, small-scale assaults on the body. Oxidation, inflammation, stress, infection, and other physiological insults take their toll, inflicting lethal damage over time that sets abnormal cell proliferation in motion.91,92 1. DNA damage. Numerous biomolecular assaults strike at the “blueprint” that cells need in order to replicate themselves accurately. DNA damage is often referred to as the “initiator” in cancer development—the first step in the onset of most cancers. 2. Excessive or chronic inflammation. Inflammatory processes trigger the release of a host of disruptive cytokines (cell-signaling molecules) that affect virtually all cellular functions. Inflammation is commonly referred to as a cancer “promoter” for this reason. 3. Disruption of cell signaling pathways. Normal communication within and between cells assures proper regulation of their healthy function. These pathways are easily disrupted by adverse events such as inflammation. 4. Alterations in the cellular reproductive cycle. Cells undergo a four-stage process as they prepare to replicate themselves. The cell cycle itself is controlled by signaling pathways that can be altered or disrupted at each of these stages. 5. Abnormal regulation of apoptosis. Apoptosis is the process of naturally “pre-programmed” cell death that prevents overgrowth of tissue. When apoptosis fails, cells may undergo uncontrolled reproduction. 6. Altered survival pathways. The flip side of unregulated apoptosis: survival of too many healthy cells, paradoxically, can endanger the host by permitting a cancer to take hold by increasing the odds of mutation and proliferation. 7. Excessive cellular proliferation. Certain hormones and other stimuli can directly trigger cells to reproduce without safe limits, especially when the preceding regulatory mechanisms have failed. 8. Aggressive invasion of healthy tissue. This is accomplished by excessive production of enzymes and adhesion molecules that “dissolve” tissue and allow the tumor to literally take root. The word “cancer” itself is derived from the crab-like appearance of fully-developed malignancies, which extend tendrils in all directions into healthy tissue.93 9. Rapid angiogenesis. Tumors require growth of new blood vessels for nourishment. They are endowed with the capacity to spontaneously generate new blood vessels just like healthy tissue. Angiogenesis in cancer tissue is a primary means by which tumors grow. 10. Metastasis. This is the migration of cancerous cells to regions of the body beyond the locus of the primary tumor. Metastases are the distinguishing features of most malignant cancers, and the typically herald the onset of end-stage disease because they disrupt otherwise healthy tissues.

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85. Wong TS, Chan WS, Li CH, et al. Curcumin alters the migratory phenotype of nasopharyngeal carcinoma cells through up-regulation of E-cadherin. Anticancer Res. 2010 Jul;30(7):2851-6.

86. Glienke W, Maute L, Wicht J, Bergmann L. Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and downregulation of survivin/BIRC5 gene expression. Cancer Invest. 2010 Feb;28(2):166-71.

87. Jutooru I, Chadalapaka G, Lei P, Safe S. Inhibition of NFkappaB and pancreatic cancer cell and tumor growth by curcumin is dependent on specificity protein down-regulation. J Biol Chem. 2010 Aug 13;285(33):25332-44.

88. Kanai M, Yoshimura K, Asada M, et al. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol. 2010 Sep 22.

89. Lin L, Hutzen B, Zuo M, et al. Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells. Cancer Res. 2010 Mar 15;70(6):2445-54.

90. Ramachandran C, Resek AP, Escal on E, Aviram A, Melnick SJ. Potentiation of gemcitabine by Turmeric Force in pancreatic cancer cell lines. Oncol Rep. 2010 Jun;23(6):1529-35.

91. Bengmark S. Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. JPEN J Parenter Enteral Nutr. 2006 Jan-Feb;30(1):45-51.

92. Bengmark S, Mesa MD, Gil A. Plant-derived health: the effects of turmeric and curcuminoids. Nutr Hosp. 2009 May-Jun;24(3):273-81.

93. Argyle DJ, Blacking T. From viruses to cancer stem cells: dissecting the pathways to malignancy. Vet J. 2008 Sep;177(3):311-23.

http://www.lef.org/Magazine/2011/3/How-Curcumin-Protects-Against-Cancer/Page-01

Real Relief for Psoriasis (and Eczema, too)

August 1, 2013

Combining conventional and natural therapies offers the best treatment…

 

Psoriasis can be painful, itchy and embarrassing…and even trigger anxiety and depression. Plus, it’s often stubbornly resistant to treatment, forcing sufferers to try one thing after another. But for the estimated 7 to 8 million Americans with psoriasis, there’s finally some welcome news…

 

A better way: The most recent research shows that by combining conventional medical care with an anti-inflammatory diet and lifestyle changes, people with psoriasis can have fewer and less severe outbreaks. Plus, psoriasis patients using natural approaches often are more responsive to medication—enabling them to use less, which reduces side effects and cost. Added benefit: These same diet and lifestyle approaches also help treat eczema, another inflammatory skin disease.

 

Best drug-free ways to ease psoriasis, based on recent research and my day-to-day work with patients…

• Limit high-GI foods. The glycemic index (GI) measures how fast different foods elevate blood sugar (glucose) and insulin in the body. The danger: High-GI foods trigger a very rapid insulin response, and high insulin levels have been linked to psoriasis. High-GI foods have inflammatory effects on the skin, making it more prone to psoriasis. Sugar and white flour are high-GI foods…vegetables, beans and whole grains are low-GI foods.
  
  What you can do: Eat meals that consist of 50% vegetables, 25% protein (fish, chicken, turkey, lean meat or eggs) and 25% unrefined carbohydrates (such as sweet potatoes or squash)—a mix that’s low GI and anti-inflammatory. Limit your intake of refined carbohydrates and dairy products. In addition, to keep blood glucose levels balanced, be sure to eat two or three snacks daily, such as fruit, nuts or seeds.

• Try fish oil. In a study conducted at the University of Michigan Medical Center, psoriasis patients who received phototherapy (a common treatment for psoriasis that involves exposure to ultraviolet-B light) and took fish oil supplements had a greater decrease in plaques (raised red patches on the skin) than participants who received phototherapy and olive oil capsules.
  
  Why it works: Fish oil may reduce tumor necrosis factor alpha (TNF-alpha), a compound involved in systemic inflammation that’s more active in psoriasis patients.
  
  What you can do: Take 1 g to 4 g of fish oil daily (with a meal).*
  
  Also helpful: Research conducted in Russia showed that supplementing daily with the antioxidants vitamin E (50 mg), coenzyme Q10 (50 mg) and selenium (48 mcg) improved symptoms in people hospitalized with erythrodermic psoriasis, the most severe form of the disease, which affects most of the body.

• Find out if gluten worsens your symptoms. Research shows that about one in seven people with psoriasis may have a sensitivity to gluten, a protein found in wheat, barley and rye.
  
  In a study conducted by Swedish researchers, 30 of 33 psoriasis patients with an antibody to gliadin (a subprotein in gluten) improved on a gluten-free diet. When the patients started eating gluten again, 18 of the 30 needed to increase their medication because of worsening psoriasis symptoms.
  
  What you can do: Ask your doctor for a blood test called the Deamidated Gliadin Peptide Antibody Test. If the test result is positive, consider eating a gluten-free diet for three months to see if your condition improves.

• Exercise regularly. Moderate exercise improves several risk factors for psoriasis, such as inflammation and obesity.
  
  What you can do: Exercise five to seven times a week, at a moderate level (such as brisk walking or even vigorous gardening), for 20 minutes each time. I also advise strength-training two times a week and flexibility exercises, such as yoga or Pilates, two times a week.
  
  Caution: Heat intolerance can be a problem for people with psoriasis (they often have a dysfunction of sweat glands due to psoriasis plaques)—so avoid exercising in warm, humid environments and keep well-hydrated.

• Lose weight. A 14-year study conducted at Massachusetts General Hospital linked a higher body mass index, or BMI (a ratio of height to weight), to a higher risk for psoriasis. Compared with people who had a normal BMI, those in the overweight range had a 40% higher risk for psoriasis…and those who were obese had a 48% higher risk.
  
  What you can do: Two of the strategies already discussed—a low-GI diet and regular exercise—can help you lower your BMI, which may minimize psoriasis flare-ups.

• Manage stress. A study from the University of Montreal linked higher stress levels to more severe psoriasis symptoms. And in research conducted at the University of Massachusetts Memorial Medical Center, patients with moderate-to-severe psoriasis who listened to guided stress-reduction exercises during phototherapy had accelerated clearing of their skin.
  
  What you can do: To help relieve tension and anxiety, take slow, deep breaths (inhaling until your lungs feel full, and exhaling until your lungs feel empty) for a few minutes several times a day. Other ways to relieve stress include meditation, yoga and tai chi.

• Sleep better. Research shows that poor sleep worsens inflammation and weakens the skin’s protective surface, which can dry it out.
  
  What you can do: Try to go to bed and wake up at the same time every day, allowing yourself seven to eight hours of uninterrupted sleep. For deeper sleep: Write down your worries at bedtime (and leave them on the dresser for the next day)…don’t eat or drink liquids one to two hours before bed…and keep your bedroom quiet and dark and at a comfortable temperature.

 

WHAT IS PSORIASIS?

Psoriasis is a chronic, inflammatory skin disease caused by an overactive immune system.

The most common form of the disease is plaque psoriasis—dry, itchy red (and sometimes painful) patches, with silvery-white scales, usually on the elbows, knees, scalp and lower back. Up to one-third of people with psoriasis also develop psoriatic arthritis, with stiff, swollen, painful joints.

*Check with your doctor before starting any new supplements—especially if you take a blood thinner or other medication or have a chronic health condition.

Source: Valori Treloar, MD, CNS, a board-certified dermatologist and a certified nutrition specialist of the American College of Nutrition. She is the founder and owner of Integrative Dermatology, a clinic in Newton, Massachusetts, that integrates conventional medicine and alternative therapies, and is coauthor, with Alan C. Logan, ND, of The Clear Skin Diet: How to Defeat Acne and Enjoy Healthy Skin (Cumberland House).

http://www.bottomlinepublications.com/content/article/health-a-healing/real-relief-for-psoriasis-and-eczema-too

Chronic Inflammation 101 - Everything you need to know (and how to eliminate it)

Wednesday, July 17, 2013 by: PF Louis

(NaturalNews) Improved hygiene habits, water clear of pathogens (though with added chemical toxins), and good plumbing have controlled infectious diseases to a minimal threat.

The medical establishment's claims of vaccinations vanquishing infectious disease is bogus. Instead, vaccines have contributed heavily to the modern day threat of autoimmune diseases and diseases from chronic inflammation.

Rather than microbial pathogens, it's the industrial toxins, toxic fake foods, and "better living through chemistry" gone crazy that are the sources of chronic inflammation leading to most disease now.

Why and how inflammation occurs

Inflammation is the body's immune response to any attack from foreign invaders, be they pathogenic microbes, synthetic chemicals, or physical impact or burns. Classic signs of acute inflammation include redness, swelling, pain, or fever and loss of appetite.

That's because sensor cells have detected a pathogenic invader or physical injury. Then a host of biochemical reactions takes place in the surrounding tissue that's affected, depending on the nature of invasion or injury.

Histamine is released, causing blood vessels to expand. Interleukins act as messengers and spotters for other cytokine killer white cells that are summoned to take action.

Chief among those are macrophages, a combination of Greek words meaning big eaters. They basically engulf foreign proteins and pathogens and their waste products. Other white blood killer cells arrive to fight off the invaders as well.

Macrophage cells may release a biochemical agent known as tumor necrosis factor alpha (TNF-alpha) to produce fever and loss of appetite. Nitrous oxide is sometimes released to increase blood flow, while clotting materials may sometimes be released to slow blood flow and clot a wound.

When there is a surplus of white blood cells in an area, pus is formed. All these immune reactions are meant to protect our tissues and restore the body to homeostasis or functional balance. They may react in different sequences, partially, or wholly according to the type of infection or injury.

These events are great for acute situations. When the body recovers, the inflammation ends. All is well. But what if these biochemical events don't stop and the inflammatory process continues unabated?

Vaccines can and often do incite extreme reactions, called cytokine storms, where an immune system tsunami overwhelms healthy neurological tissues, leading to permanent damage, disability, or death.

Less serious cytokine reactions from vaccines often lead to chronic inflammation.

Chronic inflammation is both subtle and sinister

Imagine some of the immune system reactions described going on beneath one's awareness for extended periods. No pain, but maybe a vague feeling of discomfort or feeling not quite with it.

That's chronic inflammation, and it often leads to a full blown life threatening diseases like heart failure or cancer, debilitating diseases such as Parkinson's or MS, or a chronically aggravating disease like asthma.

Chronic allergies can be indicators of an immune system gone off the rails if the allergens aren't common to others. But there are many toxins in our food and environment that act act as allergens for everyone.

The immune system doesn't recognize them, and thus reacts accordingly. This low level constant immune system activity is chronic inflammation. Cortisol built up from constant stress creates a hormonal imbalance leading to chronic inflammation as well.

What to do about it all

First, it's important to avoid synthetic chemicals that are considered sub-lethal with a low single dosage but accumulate in the body's tissues to create chronic inflammation. A good example is fluoridated water.

Kick the processed food convenience habit and eat mostly organic whole foods. Read labels and keep up with what's not good for you as well as what's good for you with Natural News. Keep in mind that one dietary approach may work for some but not others.

Don't use synthetic commercial cosmetics and deodorants. Avoid anti-antiperspirants. Get synthetic household cleansers, including dish and laundry detergents out of your dwelling and use natural products or make your own.

Stress less, sleep better, and exercise moderately. Use inexpensive turmeric, ginger, holy basil, and adaptogenic herbs liberally to effectively minimize inflammation. Whichever you choose, use it or them daily.


Sources for this article include:

http://www.mindbodygreen.com
http://medical-dictionary.thefreedictionary.com
http://www.britannica.com
www.google.com
 Articles Related to This Article:

• The Powerful Role of Omega-3 Fatty Acids in Preventing Diseases of Inflammation: The Experts Speak
• Review: Zyflamend Supplement for Inflammation; Tips on Anti-Inflammatory Foods and Herbs
• Inflammation is the cause of nearly all disease - Here's how to prevent it
• White tea, witch hazel proven by scientists to reduce inflammation and fight cancer
• Inflammation is a major reason why you can't lose weight
• A Huge Number of Illnesses are Caused by Inflammation

http://www.naturalnews.com/041228_chronic_inflammation_vaccinations_immune_system.html

Life Extension Magazine November 2011

The Inflammatory Factor Underlying Most Cancers By David Hoffnung

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

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

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

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

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 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 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.

References

1. Shin SR, Sanchez-Velar N, Sherr DH, Sonenshein GE. 7,12-dimethylbenz(a)anthracene treatment of a c-rel mouse mammary tumor cell line induces epithelial to mesenchymal transition via activation of nuclear factor-kappaB. Cancer Res. 2006 Mar 1;66(5):2570-5. 2. Renehan AG, Roberts DL, Dive C. Obesity and cancer: pathophysiological and biological mechanisms. Arch Physiol Biochem. 2008 Feb;114(1):71-83. 3. Enwonwu CO, Meeks VI. Bionutrition and oral cancer in humans. Crit Rev Oral Biol Med. 1995;6(1):5-17. 4. Liu M, Sakamaki T, Casimiro MC, et al. The canonical NF-kappaB pathway governs mammary tumorigenesis in transgenic mice and tumor stem cell expansion. Cancer Res. 2010 Dec 15;70(24):10464-73. 5. Prasad S, Ravindran J, Aggarwal BB. NF-kappaB and cancer: how intimate is this relationship. Mol Cell Biochem. 2010 Mar;336(1-2):25-37. 6. Pianetti S, Arsura M, Romieu-Mourez R, Coffey RJ, Sonenshein GE. 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