What Is Nuclear Factor-Kappa Beta?July 2006
By Julius G. Goepp, MD
How Inhibiting NFkB Helps Fight Cancer
Recent discoveries about NFkB confirm the deadly link between inflammation and cancer. It is well known that nutrients and drugs that reduce inflammation also help fight cancer.8,9 Some anti-inflammatory drugs, however, carry cardiovascular risk.10,11 Scientists hope that therapies that block NFkB may provide safe, effective action against both inflammation and cancer.
The ubiquitous presence of NFkB throughout the inflammation-cancer cycle suggests that the next breakthroughs in cancer treatment will likely center on the inhibition of NFkB and its actions. As scientists learn more about NFkB and the complex systems that regulate it, they also learn more about the wide array of substances that can inhibit its dangerous actions. For example, the anti-inflammatory drug ibuprofen inhibits not only the COX-2 enzyme but also NFkB,12 and has a well-established safety record. This drug, as well as many natural inhibitors of NFkB, will therefore play an important role in controlling the inflammatory components of tumor formation and growth.
Because the NFkB factors are active in both the cancerous cells and inflammatory cells in tumors, nutrients or drugs that can inhibit NFkB show tremendous promise as anti-cancer or cancer-preventive agents.8 Scientists believe that the combination of NFkB inhibition with drugs or cytokines that induce cancer cell death has great promise in fighting cancer.13
Because the NFkB system is also involved in producing healthy immune responses, there are concerns about its long-term inhibition. While NFkB seems to be most profoundly involved in cancer at the stages of promotion and progression,8,14 it may be possible to use inhibitors for relatively short periods. Another potential use for such inhibitors would be in combination with chemotherapy or radiation treatments, as a means of controlling the associated inflammation and enhancing the effects of those treatments.8
Nutrients That Inhibit NFkB
The search is on for safe, effective inhibitors of NFkB. One of the most exciting features of the explosion of NFkB research is that it sheds new light on the mechanisms of many familiar nutrients.
Health-conscious people are quite familiar with how antioxidants, vitamins, minerals, and essential nutrients such as omega-3 fatty acids can maintain health and prevent disease. It is becoming increasingly clear that many such compounds exert some of their beneficial effects through interactions with the NFkB system. Although the precise mechanisms vary, all of these agents work by inhibiting NFkB activation, thus preventing the expression of genes involved in inflammation and cancer development. Here we summarize familiar nutrients whose NFkB-related actions are now coming to light.
Antioxidants are known to reduce inflammation and cancer risk. The identification of NFkB as the common link to both processes may serve to explain how these substances operate. Vitamins E and C have been shown to reduce inflammatory cytokine production that is a consequence of NFkB activation.20
N-acetylcysteine inhibits NFkB, which is likely the mechanism by which it confers its health-promoting effects.21 S-adenosyl-methionine (SAMe) exerts some of its powerful anti-inflammatory effects by reducing NFkB activation.22 The potent antioxidant lipoic acid binds to and inhibits NFkB in the cell’s nucleus.23 Zinc may also exert its antioxidant effect by reducing NFkB activation.24
Essential Fatty Acids and Other Lipids
The omega-3 fatty acids are also known to reduce inflammation and decrease the production of inflammatory cytokines. Evidence is emerging that these effects occur due to inhibition of NFkB activity by eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and other essential fatty acids in this class.25-27
EPA and DHA protect the eye’s retinal cells from oxidative damage. Moreover, these fatty acids may impair the overgrowth of blood vessel cells that occurs in several retinal diseases, by reducing the production of inflammatory cytokines, vascular growth factors, and adhesion molecules, all via the common pathway of NFkB inhibition.28
Isoflavones and Phytoestrogens
Soy isoflavones and other plant flavonoids are well-established modulators of the immune system’s inflammatory responses. These phytoestrogens (plant-derived, estrogen-like molecules) are known to help reduce the risk of certain hormone-dependent cancers, as well as the risk and severity of osteoporosis.29 Researchers have shown that the isoflavone-induced inhibition of NFkB is the mechanism by which isoflavones reduce the invasiveness of breast cancer and increase programmed cell death in various human cancer cell lines.30-32 Evidence also indicates that isoflavones may act by the same mechanism to inhibit bone loss in osteoporosis.33
Some researchers have speculated that one of the reasons women live longer than men is related to the favorable effects of estrogen on up-regulating antioxidant genes often suppressed by NFkB, suggesting that the phytoestrogens might have similar effects in promoting longevity.34
From Garden to Medicine Chest
Herbs and spices from around the world have long been sought for their pleasing flavors and healing qualities. Even today, these plant extracts are valued worldwide for promoting health and fighting disease. Scientists are discovering that many of these natural agents act through the universal mechanism of inhibiting the over-expression of NFkB.
Curcumin is a compound found in a number of South Asian spices, most prominently in turmeric, a component of curry seasoning.
Curcumin has well-established antioxidant and anti-inflammatory effects.35,36 The extent to which curcumin exerts these effects by inhibiting NFkB is becoming increasingly clear.37 Curcumin acts directly within the cell’s nucleus and also acts on substances that activate NFkB. For example, it binds iron and copper in brain tissue, reducing the activation of NFkB that is associated with the production of amyloid beta proteins in Alzheimer’s disease.35
Strong evidence suggests that curcumin may fight the following inflammatory diseases: