Update on Cancer
by David Archibald, author of Australia’s Defence, Twilight of Abundance, and American Gripen: The Solution to the F-35 Nightmare
12 November 2016
A good overview of how cancers form is Douglas Hanahan and Robert Weinberg’s The Hallmarks of Cancer, published in the journal Cell in 2000. That paper has been referenced over 15,000 times by other research papers. In summary, cells go through six mutations to become cancer cells. One of those acquired traits is evading apoptosis, which is programmed cell death. In normal cells, the cell’s DNA is constantly being checked for errors. If the error can’t be fixed, the a signal is sent from the nucleus to activate the death receptors on the cell surface. A protein called FAS ligand circulates in the blood. Its job is to bind to the death receptor and trigger apoptosis through the ‘apoptotic cascade of the caspases’. The caspases are enzymes which chop up the cellular machinery, including the membrane and the nucleus, in 30 to 120 minutes, with the detritus carried off in the intercellular fluid.
Lung cancer cell during cell division
There is another class of proteins in the cell, the anti-apoptotic proteins, which have the role of stopping accidental triggering of the caspases. Possibly more than 90 percent of cancers become immortal through over-production of anti-apoptotic proteins, chiefly c-FLIP (cellular FLICE-inhibitory protein) and XIAP (X-linked inhibitor of apoptosis protein).
It turns out that we have a cellular mechanism ready to counter the over-production of anti-apoptotic proteins. This was discovered by the husband and wife team of Professor James Morre and Professor Dorothy Morre at Purdue University. Their work is compiled in a book published in 2013 entitled ECTO-NOX Proteins: Growth, Cancer, and Aging. In short, there is a cell surface protein they called cNOX that ordinary cells have which provides the energy for the production of the anti-apoptotic proteins. In cancer cells, up to 60 percent of the cNOX molecules are replaced by tNOX (with the t for tumor) molecules on a signal from the nucleus. It seems that the expression of tNOX on the cell surface is part of the programmed reaction of the cell in encountering irreparable DNA damage.
Nothing binds to cNOX, but a numher of plant molecules bind to tNOX and have the effect of inhibiting it. The tNOX molecule has two binding sites and the inhibition effect is at least an order of magnitude higher if both sites are bound simultaneously rather than just one at a time. There is a parallel with vitamin C. Our species doesn’t make its own vitamin C. We rely upon getting enough in the diet. All other mammals, apart from primates and guinea pigs, make their own vitamin C. Presumably there was an evolutionary advantage is losing the ability to make vitamin C. Similary, the tNOX molecule evolved in the expectation that certain plant molecules would always be in the human diet.
The tNOX molecule is shed into the blood. The Morres realised that if tNOX was present in the blood, that meant that there was a cancer somewhere in the body. It turns out that there are many isomers of tNOX, depending upon the organ site. The Morres commercialised a test, based on tNOX, which will detect 25 different types of cancer using 2D electrophoresis. The test can detect cancer up to five years ahead of clinical diagnosis. Two videos of the science of the blood test:
The Morres also developed an anti-cancer formulation called Capsibiol-T. This is the combination of decaffeinated green tea extract and guajillo chilli pepper at 25:1. The instructions on the bottle are to take a capsule every four hours. The basis for that dosing regime is explained in an interesting paper by the Morres from 2008. From that paper:
The rationale for developing a sustained-release form of green tea is predicated on the knowledge that the effect of EGCg is reversible. In order for cathechins to have therapeutic efficacy in selective killing of cancer cells, our findings show that the cathchins must be present in the blood at a level of about 100 nM and to inhibit tNOX continuously at that level for a period of 48 to 72 hr (Morre et al., 2000). If the EGCg is removed even after 8 hr, cancer cells in vivo resume normal rates of growth as EGCg is cleared from the blood and/or metabolized. Even in cell culture it may not survive in the media more than few hours at nanomolar concentrations. The cancer cells in vitro must be inhibited from growing for at least 48 and perhaps up to 72 hr in order for programmed cell death (apoptosis) to be induced by EGCg.
EGCg is the active molecule in green tea. The Morres also found that dosing with tNOX inhibitors prior to chemotherapy increases the efficacy of the chemotherapy by more than an order of magnitude. The same would be true for radiotherapy. Chemotherapy and radiotherapy both work by damaging the DNA of dividing cells with the result that the cells express more death receptors. Hopefully the larger number of death receptors will overwhelm the available anti-apoptotic proteins. That is why the chemo dose given is usually just short of what will kill a person. If it is not enough, the cancer will mutate around the drug and become refractory to it.
I met the Morres early last decade and we agreed to collaborate on a patent application. That formulation was broccoli sprout powder with two chilli powders, gaujillo and ancho. The active molecule in broccoli (seeds, sprouts, heads) is sulforaphane, stored in the plant as glucoraphanin. Good results were obtained in a number of cancers but unfortunately the US Patent Office knocked back the patent. Most of the results were in prostate cancer because, as a slow-growing cancer, it is usually not treated with chemotherapy. Sulforaphane has considerable promise as a cancer therapy and there is a now available a voluminous literature on its effect on many cancer types available on www.pubmed.com
There are vast differences in cancer rates between countries due to diet. Japanese migrating to the United States go to the US breast cancer rate, which is six times higher than the Japanese rate, within a generation. The difference is largely due to the higher consumption of legumes in Japan. One of the biggest differences in cancer rates is between the North American prostate cancer rate and the Vietnamese prostate cancer rate, with the former 40 times higher than the latter:
The national dish of Vietnam is pho, a bowel of meat and noodles with three side dishes – mint, bean sprouts and chilli. The bean sprout to chilli ratio is about the same as that in the patent application the Morres and I made. The low molecular weight of sulforaphane means that it will pass through cell walls more readily than EGCg which is the active component of green tea:
- Sulforaphane: 177.29 g/mol
- Epigallocatechin gallate: 458.72 g/mol
The incidence of prostate cancer and breast cancer are the same, with currently 11 percent of men in Western countries being diagnosed with it at some point in their lives and five percent dying from it, and 11 percent of women in Western countries being diagnosed with breast cancer at some point in their lives and five percent dying from it. It need not be like this.
Westerners eat a high proportion of comfort food that lacks the tNOX inhibitor molecules that we evolved to rely upon in our diet. The effect is shown in the following graph of some epidemiological variation in PSA levels:
I am on my own anti-cancer formulation and have the PSA level of a 20 year old. The highest grade commercial source of glucoraphanin is from Caudill Seeds in Louisville, Kentucky. They sell capsules of powder for the retail market and also a minimum five kilo parcel at $400 per kilo. The gut flora convert a proportion of the glucoraphanin to sulforaphane. The proportion converted can be increased by eating radish which contains the enzyme myrosinase, mimicking what happens in the plant.