Potential of fungi used in Chinese remedies for cancer treatment
by Sinthujah Jeganathan
2003
Abstract
In November 2000 a report was created by the Cancer Research Campaign to look at the role of medicinal mushrooms in the treatment of cancer.
The aim of the Special Study Module is to review and produce a report accessible to all members of the public, using the original report. In addition it will look at the history of Chinese fungal remedies which dates far back into ancient times, and has formed the basis of the research in the report. The SSM will also look into the potential of use of fungal products in the NHS as well as their advantages and disadvantages.
The major findings of the report showed that there are certain compounds found in mushrooms that have an anti-cancer effect. These compounds are known as polysaccharides. They appear to act on the host’s immune system rather than directly on the tumour. The main polysaccharides that the report focuses on are Lentinan, Schizophyllan, PSK and PSP.
These polysaccharides have undergone several clinical trials and are showing good prospects for use in Western medicine. It is just a matter of whether the Western population will accept this method of treatment.
1. Fungi
What are mushrooms?
All living organisms on this planet belong to one of five kingdoms. Mushrooms belong to the Fungi Kingdom. Fungi include organisms such as moulds and yeasts. Fungi cannot photosynthesise, i.e. use light energy to produce food, therefore it needs to obtain its material for growth by some other means. Fungi are saprophytic organisms that break down dead organic material to obtain nutrients.
Although today we think of mushrooms mainly as a food product, they actually play a very important role in nature. Mushrooms are part of the primary recyclers in nature, secreting enzymes in order to digest the organic material. Primary decomposers usually decay woody material such as logs and tree stumps, which is often why you can find a colourful array of mushrooms in these areas.
The mushroom is actually made up of a network of fine strands called hyphae. The network builds up producing large fruit bodies, which we call mushrooms. They grow to different sizes, structures and have different metabolic activities. There is thought to be well over 1.5 million different species, 12,000 of which can be classified as mushrooms and about 2,000 which are edible.
How are mushrooms cultivated?
Mushrooms cultivation is a huge commercial business. World production of mushrooms is dominated by the Chinese who produce 64% of the total production. Not only is China the major producer but it is also the major consumer of edible and medicinal mushrooms. Because of the large demand of medicinal mushrooms it is expected that China will be at the forefront of developing new technology and methods for mushroom cultivation.
Current mushroom cultivation is already an advanced science. There are three major cultivation methods used at the moment, the first is spawn production. ‘Spawn’ are a few cells from the organism which are extracted and then put into suitable growing conditions and allowed to ferment. Also log culture is very popular, although time consuming and laborious. This involves growing saprophytic primary decomposer mushrooms on logs. Enriched sawdust culture involves growing the fungi in nitrogen enriched sawdust or wood chips under sterile conditions. This method has a shorter production time and produces higher yields than growing from a log culture. So with China leading the way in medicinal mushroom cultivation, any mushroom thought to have a medicinal effect on cancer can easily be produced at a very large scale.
How were they used in history?
Mushrooms have always been used throughout history as a flavoursome and nutritional food, various civilizations have learnt by trial and error which mushrooms are edible and which are to be avoided. They are used all over the world since they are considered to be a good source of protein, fibre and vitamins, all essential for the growth, development and maintenance of health in humans.
However in the Far East both edible and non-edible mushrooms have been used for medicinal purposes for several thousand years. They were often rare species obtained from forests. They were not usually used whole but used as concentrates, liquors or powders in health tonics, teas and soups. Today many of the rare species of mushrooms are artificially cultivated on a large scale.
2. Cancer
What is cancer?
Every organ in the body is made up of millions of individual cells that are able to balance the rate of cell death along with the rate of cell production. Sometimes a stimulus may occur causing the organ to produce more cells. Hence the rate of cell production is greater than the rate of cell death, this is called hypertrophy. However rate of cell production can be greater than rate of cell death without any stimulation, this is causes cancer. The cells continue to reproduce, disrupting the normal function of the organ, and if left long enough, can cause death (Eales 1997).
The table below shows some of the common properties of tumour cells.
Tumour cells:
Fail to respond to signals which normally control cell growth and
tissue repair.
Exhibit independent growth, i.e they do not require outside stimulus.
Invade normal tissues and, unlike normal cells, their growth is
not inhibited by other tissue.
Metastasise, i.e. they are capable of spreading into distant
organs through the lymphatic and blood circulation and there establish a new
location for growth.
(Table adapted from textbook Eales 1997)
Cancer is thought to be caused by carcinogens, these are cancer promoting substances. These can be either physical carcinogens; such as X-rays and UV light, chemical carcinogens or viral carcinogens which disrupt the hosts genetic material (Eales 1997).
How is cancer treated?
There are two main methods of treating cancer in developed countries today, they are radiotherapy and chemotherapy.
Radiotherapy involves shooting a measured dose of ionizing radiation at the tumour. The treatment should result in the removal of the tumour with as little damage to surrounding cells as possible The ionizing radiation can be in the form of X-rays and its aim is to damage the DNA, genetic information, in tumour cells so they are unable to divide (Miller and Kearsley 1999).
However radiotherapy, like many other forms of therapy, causes side effects. Complications that can occur with radiotherapy are dose related. So higher the dose, greater chance of complications occurring. There are two types of side effects:
An example of an acute side effect is alopecia, which usually occurs with radiotherapy to the brain. Most of the acute side effects are reversible within a few weeks to a month. Late side effects however are usually irreversible. Since large doses of radiotherapy are likely to cause late side effects, radiotherapy is given in several small doses (Barton 1999).
Chemotherapy is the use of chemicals that have specific toxic effects and selectively destroy cancerous cells (website: Online Medical Dictionary). Most chemotherapy is usually injected directly into the vein so it can enter the bloodstream quickly. Chemotherapy is most effective when combined with surgery and radiotherapy. It is usually given at the maximum dose possible and in a suitable schedule in order to control or cure the cancer. Again chemotherapy has side effects which include: nausea, vomiting, alopecia and general drowsiness. Among the more serious side effects are:
Even though the current methods for treating cancer are effective, but not without side-effects.
How does the body defend itself against cancer?
This section will give a brief overview of what goes on in the body when a foreign body enters it. There are many types of cell that are present in the blood whose job is to fight off disease in the body. These cells are collectively known as the immune system.
There are many cells and hormones part of the immune system, in this section we will be looking at:
- Lymphocytes
- Hormones in this immune system
- Macrophages
Lymphocytes
T Cells
T cells become activated when an antigen binds to a glycoprotein. This glycoprotein’s are called Major Histocompatibility Complexes (MHC) and are found on the membranes of cells. The diagram below shows an image of a cell membrane. The cell membrane is shown in blue, with the glycoproteins at the base of carbohydrates.
Diagram 2.1: 3D Structure Of Cell Membrane
(Image taken from website: Dawson College)
There are two major classes of MHC proteins; Class I and Class II MHC proteins. Class II MHC proteins are found in the cell membrane of antigen-presenting cells , which activate T cells. Examples of antigen-presenting cells are fixed and free macrophages. These cells will be processing antigens such as viruses and bacteria. T cells have receptors which bind specifically to antigen-presenting cells. Once this has happened the T cell divide producing more T cells and memory T cells. Memory T cells act if the same antigen enters the body, so this time it can produce the specific T cell again rapidly to fight off the antigen.
There are three main types of T cell:
- Cytotoxic T cells -one of the main functions of this type of cell is cytotoxic cell death is to tell the cell when to die, a process called apoptosis. This is an important process in the prevention of tumour growth.
- Helper T cells - two major effects of the helper T cell is to stimulate activity of the natural killer cell and increase B cell division helping to get rid of the antigen.
- Suppressor T cells - these secrete suppression factor, which effectively tell T and B cells to stop what they are doing, bringing a close to the immune response.
B Cells
B cells are activated when antigens that are ‘free-floating’ in the blood bind to antibodies on the surface of B cells. The B cell is then said to be sensitized. It causes Class II MHC proteins to appear on the surface of the B cells. A helper T cell then binds to the MHC complex on the sensitized B cell, causing the B cell to secrete cytokines that promote:
- Activation
- Division - also producing memory B cells.
- Antibody production- cytokines will release these antibodies which have the same target as sensitized B cell, this all happens to increase the immune response.
Natural Killer Cells
These are also a type of lymphocyte that kill foreign cells (not belonging to the organism), virus infected cells and cancer cells. Cancer cells show tumour specific antigens on their cell membrane, NK cells recognize them and then destroy the cell. Cancers develop when the cancerous cells do not show that tumour-specific antigen or it is ‘covered up’ in some way. These cells are said to undergo immunological escape.
Macrophages
Macrophage can be fixed onto tissue in the body or free floating in the blood stream. They eliminate pathogens by either ‘eating’ them or releasing toxic chemicals such as tumour necrosis factor and nitric oxide.
Hormones
Interleukins - as all hormones, interleukins are chemical messengers. Interleukins increase the T cell’s ‘awareness’ of antigens on the macrophage cell membrane. They stimulate the activity of B cells and hence antibody production. They also act similarly to the suppressor T cells, telling the system when to ‘stop’. There are many types of interleukin, two of the most important being- IL-1 and IL-2.
Interferons - make the cell and the surrounding cells that secrete them resistant to viral infections. They also have other benefits such as stimulating NK cells, and so are useful in fighting cancer.
Tumour Necrosis Factor -this is secreted by activated macrophages and function is to slow tumour growth and kill tumour cells. It also increases T cell sensitivity to interleukins.
Colony Stimulating Factor - produced by active T cells, stimulate the production of blood cells, T cells and B cells. (Martini 2001)
Diagram 2.1: Summary Of The Immune Response
(Image taken from textbook: Martini 2001)
3. Medicinal Effects of Mushrooms
How can mushrooms help prevent cancer?
It must be noted that it isn’t the actual mushrooms but the components of the mushroom that have the anti-cancer effect. The most relevant compound, and the one being looked at in this report are polysaccharides.
Polysaccharides are compounds that are branched or unbranched chains made of more than ten monosaccharides, linked by glycosidic bonds. Monosaccharides are simple sugars for example, glucose. Some examples of polysaccharides are starch, glycogen and cellulose. The monosaccharides undergo a condensation reaction to form long chain, either single or with branches. (Boyle 2000)
Diagram 3.1: Diagram showing how two monosaccharides bond.
(Image taken from textbook Boyle 2000)
There have been several anti-tumour polysaccharides obtained from mushrooms. Polysaccharides are usually obtained from the cell wall of the fungus (Wasser 2000). In this report we will be looking at four in detail, Lentinan, Schizophyllan, PSK and PSP. These polysaccharides are the ones that have been considered the most medicinally important and have undergone extensive clinical trials. Although the exact mechanism of action of these polysaccharides are unknown, what is known is the effect they have on the immune system. The diagram below shows an example of a beta-glucan polysaccharide, made up of glucopyranose (a form of glucose) units.
Diagram 3.2: Diagram showing Beta-glucan polysaccharide
|
|
(Image taken from review article: Medicinal mushrooms)
Both Lentinan and Schizophyllan are examples of pure b-D-glucans. b-D-glucans are polysaccharides made from D-glucose monosaccharides. The exact mechanism they have on the tumour cells are unknown, except for the fact they act indirectly promoting the immune system rather than directly attacking the cancer cells. Since they act on the immune response of the host they are known as biological response modifiers (BRM). BRM’s cause no harm or place any additional stress on the body, helping the body to adapt to the environment. All the polysaccharides discussed in this section can be described as BRM’s.
The diagram below shows a flow diagram giving a summary of the effects b-glucan polysaccharides have on the immune system.
Diagram 3.3: Likely Effects Of Proteoglycans On The Immune System
(Flow chart modified from website: Thorne)
.jpg)
