Roll of nutrients in metabolic alteration of cancer cells

diet against cancer cells
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What is the best diet to stay healthy and disease free? The answer is not as easy as it seems- this is a debate far from settled. Of course, advances in mankinds’s understanding of nutrition over the years, if not decades, have given us a reasonable idea of what’s good and healthy.

The consensus is 45-60 per cent carbohydrates, 20 per cent proteins and 20-30 per cent fat, together with adequate vitamins and micronutrients, constitute a balanced diet.

Glycolysis, ATP and cutting sugar from diet

sugar and cancer cells

Sugar feed cancer cells

Normal cells get their energy through an oxidative process while cancer cells use a fermentation process that involves glycolysis. Glycolysis is the name given to the metabolic pathway that uses sugar as a fuel and converts it under conditions of low oxygenation- anaerobic respiration- into ATP (adenosine triphosphate), which in turn is the key biochemical component that allows cells to keep running. It is necessary both for intracellular energy transfer and also for DNA replication. ATP depletion therapy is an approach that is getting serious attention from mainstream researcher (1).

The first energy-depletion strategy is so simple by cutting sugar from the diet completely. We can eat apples, grapes, oranges, etc. the fructose in these products is less bio-available than glucose or sucrose. Also, these fruits are powerhouses of other healthy phytonutrients (plant-based nutrients) which can help fight cancer. So sugar is out while raw organic fresh fruit is in. An herbal sweetener Stevie is also healthy (1).

cancer cell

Cancer cell

ATP breakdown research

There is the ATP itself. One group of Indian researchers has formulated the thesis that one way of attacking cancer is to inhibit ATP with a substance called methylglyoxal. This is a natural breakdown product that we produce in our bodies during glycolysis. In 2001, Indian biochemist Professor Manju Ray trialed methylglyoxal on 19 patients with ‘very advantage stages’ of cancer.

Of these, all of whom would normally have died within months, only three did in fact die; five had their cancers stabilized and eleven were effectively cured.

Further studies resulted in an overall cure rate of 70% in cancer patients who were diagnosed as terminally ill. It is very likely the cure rate would have been higher if taken at earlier stages. Even better, methylglyoxal, unlike other chemotherapy drugs, is virtually non-toxic for normal cells.

Methylglyoxal has every appearance therefore of being a safe and highly effective treatment for cancer. In short, all those women who sold their houses in order to afford Herceptin should really have been trying to get their hands on methylglyoxal. Our urine contains methylglyoxal (1).

Cancer cells glucose consumption

Good cells perform their physiological activities only at the right time and in the right place. When removed from their natural surroundings they self-destruct – an event that is termed anoikis (Greek for homelessness).

Not so cancer cells: they survive, invade other tissues and continue to grow in unfamiliar territories. Schafer et al (2009) (2) show that cancer-inducing oncogenes may protect cells from anoikis by maintaining the cells’ glucose consumption.

Their work demonstrates that the death of normal ‘away-from-home’ cells is caused by starvation, and strongly connects cellular metabolism to cancer.

Anoikis occurs when cells detach from the basement membrane or the extracellular matrix, both of which provide them with survival signals (3).

Originally, anoikis was thought to be executed by apoptosis – a programmed cell death set off by several different cues, which results in cell fragmentation and elimination.

Yet it turns out that blocking apoptosis does not prevent anoikis because detached cells die anyway (4). Moreover another process, autophagy – in which the cell digests some of its own components – is observed in anoikic cells (5). If autophagy runs its full course, cells kill themselves by self-consumption but, at first, autophagy may help cells to survive starvation.

This prompted Schafer et al. (2) to investigate whether starvation is a feature of anoikis and, indeed, they showed that, when detached from the extracellular matrix, breast epithelial cells reduce their glucose uptake and energy production.

Cancer cells proliferationCancer cells proliferation and invasion

Cancer cells have an unbridled capacity for proliferation and invasion. Thus, cancer cells escape anoikis or, viewed another way, anoikis prevents cancer. Several oncogenes are known to hinder anoikis (3) but the mechanisms by which they do this remain obscure.

One oncogene, ERBB2, encodes the epidermal growth factor receptor (4), a cell-surface protein that is activated in approximately 25% of breast cancers. On the basis of their data linking glucose uptake with cellular detachment, Schafer et al (2) asked whether ERBB2 expression might prevent anoikis in detached breast epithelial cells by affecting energy metabolism.

They grew normal and ERBB2-overexpressing breast epithelial cells in a three-dimensional culture system that mimics normal mammary gland structure.

The breast cells spontaneously form globules that are made up of a single layer of cells surrounded by a basement membrane. These globules reliably emulate mammary gland sacs (or acini), which usually have a hollow center because the inner cells that have detached from the external basement membrane have been eliminated by anoikis – an essential process for the formation of mammary gland (6). By contrast, filling the centre of the acini with cells is a feature of breast cancer.

Using this culture system, Schafer et al. (2) show that ERBB2 expression rescues detached cells from energy depletion by maintaining their glucose uptake, specifically by activating the cancer-inducing P13K/AKT pathway (2). He studied that the P13K/AKT pathway activates glucose uptake (7) and protects cancer cells from starvation (8).

Once in the cell, glucose may be metabolized through several pathways, including glycolysis, in which it is broken down to pyruvate to generate ATP, the cell’s energy currency, and NADH, a mediator of ATP production. Pyruvate is routed to the mitochondria where, in the presence of oxygen, it is metabolized to produce large amounts of ATP.

Although oxygen is essential for generating maximum yield of energy from glucose breakdown, it can also fatally damage the cells by contributing to various forms of oxidative stress.

Glucose helps to prevent this oxidative stress—for a small price in bioenergy, glucose bypasses the initial steps of glycolysis and enters the pentose phosphate pathway. This produces less ATP but generates NADPH, a powerful mediator of antioxidative reactions that protects cells from oxidative damage (9, 10).

In an interesting twist, Schafer et al. (2) note that anoikis can be prevented in normal, detached, glucose-starved cells if they are given antioxidants, showing that it is increased oxidative stress rather than decreased glycolysis that induces rapid anoikis. Moreover, the authors show that oxidative stress caused by a lack of glucose uptake prevents the metabolism of fatty molecules (which are a compensating energy source) and so exacerbates starvation.

Schafer and colleagues’ observations (2) that ERBB2 overexpression sustains matrix-detached cancer cells by maintaining glucose uptake adds to the evidence connecting metabolic alterations to cancer progression (11). And their finding (2) that induces anoikis in matrix-detached cells calls into question the rationale of treating cancer with antioxidants.

Apoptosis induction may be the pathway of choice for executing anoikis, but given that blocking apoptosis does not protect cells from starvation, there may well be alternative anoikis-inducing pathways that await discovery.

folic acid food

Food rich with folic acid

Deficiency of folic acid

It is recognized that many if not most people are deficient in folic acid, which is present in green leafy vegetables and, more and more commonly, in fortified breakfast cereals. The drinking of orange juice or any other fruit juice containing vitamin C enhances the absorption of folic acid from food. Many people are taking folic acid supplements of up to 1000mcg. Alcohol and drugs can have a negative impact on our folic acid intake. Folic acid is necessary for healthy cell division and to repair damage to DNA.

It is known that most cervical dysplasias and other pre-cancerous conditions leading up to full-blown cervical cancer will correct themselves once adequate folic acid intake is established. Many other cancers have been associated with low levels of folic acid.

A good level of folic acid intake is known to be of value in treating many different forms of cancer. However, it is also difficult to get enough folic acid in your diet from vegetables alone. Actually liver is the food with the highest folic acid content, but supplementation is still advisable (1).

vitamin c rich food
Vtamin c concentration

Deficiency of vitamin C

Another candidate is vitamin C. it has been suggested that a deficiency of vitamin C is a possible cause of cancer. Many think of it as simply an antioxidant. In fact, vitamin C is one of the fundamental elements for our physical biochemistry. It is vital for a vast range of biochemical and enzymatic reactions, not to mention its role in maintaining the collagen that holds everything together.

Scurvy is the result of things not holding together. Interestingly, some of the symptoms of leukemia are identical to scurvy and the author (1) knows of one anecdote in which a young child with leukemia was cured after taking in large doses of vitamin C. And there are a growing number of people who swear that intravenous vitamin C, three times a week for a number of weeks, has cured them of cancer.

To restate the vitamin C argument, the main reason for supplementing with the vitamin is that most animals make vitamin C, and they make it in very large quantities. When they are ill they make it in even larger quantities. To extrapolate these results in human terms, given our size and weight the levels of vitamin C we would probably be producing if we could produce it range from 8-12 grams on a good day to 100 grams on a bad one.

There must be a reason why these animals are producing so many vitamins C. if we are not producing or taking in anything like this level then we must be deficient.  Therefore when we are ill it makes sense for us to take it in as large a quantity as we can, and in the form of L-ascorbic acid, which is mildly acidic, or in the form of sodium ascorbate (but not calcium ascorbate), which is not acidic at all (1).

Percy WatsonCancer: Cause and Cure

Percy Watson wrote an extremely important book, Cancer: Cause and cure, which details his clear demonstration that the main cause of cancer is the way we grow our food. He discovered that highly acidic chemical fertilizer superphosphate in addition to depleting the soil of minerals also killed the soil bacteria and earthworms necessary for the healthy regeneration of the soil.

The result was- and remains- that the majority of our food contains excessive phosphorus and is deficient in calcium, magnesium, selenium, zinc, cobalt and other trace minerals. It is well known that cancer incidence is greater in areas with low selenium levels in the soil.

High selenium intake is associated with reduced cancer risk. This is additional support for the idea that trace mineral deficiency could be a cause of cancer. All of this leads strongly to the conclusion that the quality of the food we eat- and consequently the quality of our health- is very dependent on the quality of the soil our food grows in. For this reason, organic food should be a standard part of our diet, and we need to be very protective about what food companies can call ‘organic’ (1)

Enzyme called nuclear factor-kappa B

One approach focuses on a Cancer: Cause and cure enyzme called nuclear factor-kappa B (NF-kB). When this enzyme is present in increased quantities then cell division is encouraged. If a way can be found to inhibit this enzyme then cell division will be reduced or even blocked entirely. In fact, there are a number of natural substances that can achieve this objective. We have, in fact, met most of them before. The usual suspects, in this case, include vitamin C, vitamin D, curcumin and one or two other substances (1).

Curcumin and cancer cells

Curcumin and cancer cells

Curcumin is an extract from herb turmeric and it is getting very serious attention from cancer researchers. It should be mentioned here that curcumin is now known to attack cancer in other ways- not just through its inhibition of angiogenesis.

For the cancer patient, pure curcumin is required and a dose of 4-8 grams a day is recommended. However, curcumin capsules are useless as the curcumin need to be dissolved in fat before being ingested. The best way to take it is to buy curcumin powder and dissolve it in warm coconut milk or cream and drink it. Curcumin should not be used in the case of any brain cancer as it may cause cancer to swell.

Curcumin works synergistically with feverfew herb, which is also not soluble in water so it too needs to be dissolved in fat (effective dose around 4 grams per day) (1).

inositol hexaphosphateIP6 and cancer

IP6 is a chemical called inositol hexaphosphate and is found naturally in high fiber food such as beans, brown rice, and wheat bran. A number of animal studies, but as yet no human studies, indicate that it is extremely effective against a wide range of cancers.

It appears to work against all cancer cells by normalizing them- tuning them back into normal cells. Interestingly, it has been found to work against every kind of cancer cell studied in animals- and there is no known toxicity. According to Dr. Abdul Kalm Shamsuddin, professor of Pathology at the University Of Maryland School Of Medicine in Baltimore, who deloped IP6, someone with cancer should be taking 4800-7200 mg of IP6 and 1200-1800 mg of inositol.

One reputable brand is Cell Forte. It is widely available on the internet. Dr Samsuddin recommends two scoops in the morning and two in the evening.

  <h2>Vitamin E and cancer</h2>
<p>Vitamin E is a substance viewed with some disfavor in relation to cancer. There are some suspicions that standard forms of vitamin E may actually protect cancer. However, there is one form of vitamin E, alpha-tocopherol succinate, which has been found to promote apoptosis. A good source for this vitamin is Life Extension Foundation at <a href="https://web.archive.org/web/20111123151434/http://www.lef.org/" rel="nofollow">www.lef.org</a> (1).</p>
<p>Vitamin E and cancer

Vitamin E is a substance viewed with some disfavor in relation to cancer. There are some suspicions that standard forms of vitamin E may actually protect cancer. However, there is one form of vitamin E, alpha-tocopherol succinate, which has been found to promote apoptosis. A good source for this vitamin is Life Extension Foundation  (1).

Cayenne pepper
Cayenne pepper

Cayenne pepper has anti-cancer effects

Cayenne pepper is known to be very effective for heart problems and can even stop a heart attack. Herbalist Dr. Richard Schulze also claims that it has powerful anti-cancer effects. In March 2006, the journal Cancer Research published the results of a study undertaken at Los Angels’ Cedars-Sinai Medical Centre demonstrating that capsaicin, the ingredient that makes pepper hot, has the effect of causing cancer cells to die by inducing apoptosis (programmed cell death).

Schulze recommends one teaspoon of organic cayenne pepper, or an equivalent number of drops of a good cayenne pepper tincture, in a glass of hot water three times a day for almost everything. Cayenne also has the immediate impact of widening the blood vessels, which allows more blood and oxygen to reach distant sites.

And if none of these appeals you could simply chop up some fresh ginger and let it steep for a while in boiling water. Drink the resulting ginger tea. This too will help persuade cancer cell to become normal (1).

Cancer cells appear to take advantage of an enzyme that breaks down stored fats in cells to support their aggressive growth and spread, a discovery that could lead to new cancer treatments.

Metabolism of cancer cells

Researchers have long known that the metabolism of cancer cells is different in many ways from the metabolism of normal cells. However, little is known about whether and how these metabolic changes actually drive the behavior of cancer cells. NCI supported scientists analyzed the activity of a group of metabolic enzymes called serine hydrolases in cancer cells grown in the laboratory that varied in their aggressiveness.

They found that two serine hydrolase enzymes were consistently more active in aggressive cancer cells. Although one of these enzymes were already suspected to play a role in cancer, the other—known as monoacylglycerol lipase, or MAGL—had not been associated with cancer previously.

MAGL breaks down intracellular triglyceride fats to fatty acids and glycerol. In their research, the scientists studied aggressive and nonaggressive cancer cells from three different tumor types, including melanoma, ovarian cancer, and breast cancer. In addition, they found that MAGL activity was higher in tumor tissue from high-grade ovarian cancers compared with tissue from benign ovarian tumors or low-grade ovarian cancers.

The researchers also found that increased MAGL activity in aggressive cancer cells was associated with increased levels of free fatty acids (fatty acids not attached to other molecules), suggesting that MAGL plays a role in controlling free fatty acid levels in cancer cells. MAGL does not, in general, control free fatty acid levels in normal cells, suggesting that cancer cells co-opt, or highjack, this enzyme’s function to support their needs (12).

Overall, the results show that cancer cells can co-opt MAGL’s function to increase the supply of free fatty acids, which they use to support their malignant behavior. The results also suggest that a high-fat diet might promote the growth and spread of cancer cells that do not use MAGL in this manner. In addition, the findings suggest that drugs that target MAGL might someday be used for cancer therapy (12).

Conclusion

Human brainpower and happiness are intimately linked to what we eat- with some food providing an instant boost to our mental acuity and mood. Cancer is a process that starts off with poor diet, poor nutrition, the presence of toxins, and seemingly minor problems with a number of aspects of our general health. Many of the carcinogens are breakdown products of food, for example, nitrosamines. Low-fiber diets lead to a decrease of transit time through the bowel, thereby increasing exposure to carcinogenic substances.

References:

  1. Chamberlain. J . In: Cancer  Recovery Guide. Clairview Books, Cromwell Press Limited, Trowbridge,Wiltshire, 2008.
  2. Schafer, Z.T. et al. Nature 461: 109-113 (2009).
  3. Frisch, S.M & Screaton,R.A. Curr.Opin.Cell Biol 13:555-562 (2001).
  4. Debnath,J. et al. Cell 111:29-40 (2002).
  5. Lock, R, & Debnath, J. Curr,Opin.Cell Biol. 20: 583-588 (2008).
  6. Nelson, C.M & Bissell, M. J. Annu. Rev. Cell Dev. Biol. 22: 287-309 (2006).
  7. Plas, D & Thompson, C.B. Oncogene 24: 7435-7442 (2005).
  8. Kalaany, N.Y & Sabatini, D.M. Nature 458: 725-731 (2009).
  9. Bensaad, K et al. Cell 126: 107-120 (2006).
  10. Herrero-Mendez, A et al. Nature Cell Biol. 11: 747-752 (2009).
  11. Tennate, D.A et al. Carcinogenesis 30: 1269-1280 (2009).

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Michael Richardson

Michael Richardson

I am a nutritionist and healthcare practitioner with over 10 years of experience. I am a medical article writer, blog writer. My passion is to help people. My favorite quote is:  “Let food be thy medicine and medicine be thy food.” ― Hippocrates

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