Otto Warburg was one of the leading biochemists of the 20th century. He investigated the mechanism of energy metabolism used in humans and was awarded the Nobel Prize in Medicine and Physiology in 1931. His investigations explored how cells utilized glucose to generate energy(1)(2), particulary, how cancer cells fundamentally differ in the way they generate energy compared to healthy cells. He observed that healthy cells generate energy in the presence of oxygen, while cancer cells generate energy in the absence of oxygen. From this observation, Warburg remarked, "In the end, it can be concluded that the occurrence of cancer is dependent on whether cells can use oxygen to breakdown glucose or not" and stated, "Give cells oxygen and they will be normal, remove oxygen and they will become cancerous". The phenomenon that describes this irregular metabolism by cancer cells became known as the "Warburg effect", and is often cited in cancer research papers. Unfortunately, Warburg himself could not elucidate the mechanism behind this unusual phenomenon.
In 2006, the Cancer Research Team in the Department of Medicine at the University of Yamagata(3) observed that cancer cells did not seem to use oxygen even if it was available. They published this work in the American Medical Journal, which concluded that by forcing cancer cells to use oxygen, the cells undergo apoptosis (suicidal cell death) and that this could be used as an anti-cancer therapy.
Warburg proposed that cancer cells given oxygen would revert back to their normal healthy state. It has since been shown, however, that cancer cell metabolism does not consume oxygen even if it is available. What then is the reason that cancer cells do not require oxygen for their metabolic processes? This question remained a mystery for long time, until we discovered that it not the case that cancer cells simply choose not to use oxygen but rather that they cannot use oxygen. A simplified explanation is described below:
Various events such as inflammation may decrease cellular metabolism, which leads to an energy shortage in the cells. In order to produce energy, cells preferentially use glucose rather than oxygen (glycolysis). During glycolysis, various toxic by-products are released. In particular, extremely toxic substances such as the sulphur-containing gases, hydrogen sulphide and methanethiol, react with iron present in the active centre of heme proteins (to be specific, it is the sulfur atom in the gas that reacts with the iron). Normally, oxygen binds iron in the heme protein, which then acts as an oxygen transporter in the body. However, oxygen is unable to bind to iron in presence of sulfur-containing gases and as a result, cells cannot utilize oxygen.
Warburg once claimed, "Give cancer cells oxygen, and they will become normal cells". This theory in and of itself was not incorrect, however, it became clear that the sulfur atom in sulfur-containing gases preferentially bound to the iron atom in heme proteins, which is critical for oxygen transport. Hence, cancer cells can not utlize oxygen even if it is present in the environment.
We discovered that as cancer cells generate energy, sulfur-containing gases such as hydrogen sulfide and methanethiol are released around the cells. Warburg described the difference between normal cells and cancer cells as the following: "Imagine there are two engines (healthy cells and cancer cells). Imagine one engine is using coal and is going through complete combustion and the other is working through incomplete combustion. Even those who are ignorant about the structure or use of engines would know the difference between the two. For example, the two can be differentiated based on the smell generated from their engines" (excerpt from Cancer Research Race (2)).
Recently, dogs that can detect the presence of cancer by nothing more than smell has made news headlines. There is no doubt that cancer cells possess a unique smell. It has also been reported that the accuracy of tumor identification drastically decreases if the tumor samples are dried. This demonstrates that the odor emenating from the cells is indeed volatile. Employing the example from Warburg, the smell from cancer cells is like the smell of incomplete combustion. This smell turned out to be the sulfur-containing gas that we have discovered.
The toxic sulfur-containing gases such as hydrogen sulfide and methanethiol do not remain at the original site of the cancer but rather disperse into the surrounding mileu. The later the cancer is discovered, the more the sulfur-containing gases will spread within the body, and the higher the toxicity to to the organ functions within the body. Sulfur-containing gases in particular place a heavy burden on the liver, which is responsible for detoxification, and the lungs, which exchange toxic gases for fresh oxygen. From a cellular level, the gasses cause the heme proteins to lose their ability to transport oxygen, and consequently, a critical source of energy is removed from living systems. Early detection of cancer is therefore essential in order to avoid build-up of the sulfur-containing gases which negatively affect the entire body.
Simply removing cancer from the body does not guarantee that relapse will not occur, since metastasis is a possibility. Once metastasis has been confirmed, there is increased anxiety that the cancer will spread and establish itself in other areas, at which point the disease is often feared to be incurable. Cancer cells possess the ability to survive under any conditions as long as glucose or other sugars are present. Hence, there has not been any effective way to stop cancer cells once they circulate, proliferate and become active.
The situation is changing, however. Research is now being done on the induction of natural healing by simultaneously reverting the liver and lung to their original state, while restoring the functions of cancer-attacking immune cells by decreasing or diluting the sulfur-containing gases within the body.
We did not use any special anti-cancer drugs for this research. After thorough consideration of the underlying cause of cancer proliferation and metastasis, we realized that we could sufficiently suppress the growth of cancer cells using existing compounds or drugs; elaborate chemotherapeutic drugs would no longer be necessary. Please refer to our paper for details.
The cause of cancer has been said to be genetic, and indeed cancer cells possess many genetic mutations. However, we must consider why genes mutate in the first place. It is because the existing genes (that participate in normal physiological functions) specialize in using oxygen for energy production. These genes synthesize proteins that are required for energy production using oxygen. In cancer cells, however, oxygen cannot be used for energy production, and thus the cells require sugar to generate energy. Therefore, the molecular structure of the proteins needs to change in a way that is conducive to energy production in cancer cells. Thus, cancer-specific proteins are produced, and in order to produce these proteins, the genes need to be mutated.
Our research team is exploring a novel cancer treatment that negates the cause of cancer proliferation and metastasis by removing the toxic sulfur-containing gases. In the near future, as we continue to pursue this research we sincerely hope that the concept of cancer as an incurable disease will be a concept of the past.
| （References） | |
1. | WARBURG O : On the origin of cancer cells.: Science. 1956 Feb 24;123(3191):309-14. PMID:13298683 |
2. | Racing to the Beginning of the Road. The Search for the Origin of Cancer Robert A.Weinberg |
3. | Critical role for mitochondrial oxidative phosphorylation in the activation of tumor suppressors Bax and Bak Arata Tomiyama, Shinobu Serizawa, Ken Tachibana, Kaori Sakurada, Hirotsugu Samejima, Yoshiyuki Kuchino, Chifumi Kitanaka Journal of the National Cancer Institute;11/2006; 98(20):1462-73. DOI: 10.1093/jnci/djj395 |
Arata Tomiyama, Shinobu Serizawa, Ken Tachibana, Kaori Sakurada, Hirotsugu Samejima, Yoshiyuki Kuchino, Chifumi Kitanaka
Journal of the National Cancer Institute;11/2006; 98(20):1462-73. DOI: 10.1093/jnci/djj395