In research to be published in the Journal of Biological Chemistry, Dr Cornelia de Moor of The University of Nottingham and her team have investigated a drug called cordycepin, which was originally extracted from a rare kind of wild mushroom called cordyceps and is now prepared from a cultivated form.
Dr de Moor said: “Our discovery will open up the possibility of investigating the range of different cancers that could be treated with cordycepin.
(http://www.bbsrc.ac.uk/news/archive/2009/091223-pr-new-insights-mushroom-derived-drug-for-cancer.aspx)
(http://www.sciencedaily.com/releases/2009/12/091223094729.htm)
Purpose of this published study is scientific information and education, it should not be used for diagnosing or treating a health problem or disease. This website is designed for general education and information purposes only and does not substitute for professional medical advice, examination, diagnosis or treatment.
Mushroom polysaccharides and Immune system
Administration of polysaccharides fractions CI-P and CI-A derived from Cordyceps in doses of one to ten mg/kg per day, demonstrated substantial antitumor activities in mice with sarcoma 180. An alkali soluble polysaccharide, named CI-6P, derived from the species Cordyceps sobolifera, yielded remarkable results against murine sarcoma 180 when administered in doses of 10 mg/kg/day. (Mizuno 1999) In a related study, B-(1- 3)-D-glucan, fraction CO-1 and the galactosaminoglycan fraction CO-N, derived from Cordyceps ophioglossoides, inhibited the growth of ascitic Sarcoma 180. Increased immune functiondetected as well, quantified by an increase in carbon clearance activity. (Ohmori 1998, 1999) In one study, the CO-N fraction of Cordyceps ophioglossoides showed a remarkable effectiveness against the sarcoma 180 cell line, which is a reference solid tumor used for laboratory assays of anti-tumor effectiveness. A single dose of only 0.5 mg/kg-injected i.p into mice inhibited tumor growth by an astounding 98.7%! (Ohmori et al 1986). This nearly complete tumor inhibition certainly heralds some positive potential in the development of new anticancer drugs and treatment modalities.
It is well established that numerous fungal derived simple- and protein-bound polysaccharides exert a significant potentiation of immune function. (Wasser, 2002) This is thought to be one of the major mechanisms of antitumor action by Cordyceps. Among the multiple polysaccharides produced by Cordyceps, beta-d-glucans are one class of these polymers that have been shown to increase both innate and cell-mediated immune response. These polysaccharides increase the production of such cytokines as TNF-a, interleukins, and interferons, NO, and antibodies by the activated immune cells. This activation of immune response may be triggered by polysaccharide binding to specific receptors on the surface of the immune systems cells, called the CR3 receptor. (Smith et al 2002). They are also thought to be involved in cell-to-cell communications, perhaps by acting as messenger molecules.
Many clinical studies, conducted in China and Japan with cancer patients (Wang et al 2001) with whom Cordyceps was used, have yielded positive results. In one study of fifty patients with lung cancer who were administered Cordyceps At 6 grams per day in conjunction with chemotherapy, tumors were reduced in size in 46% of patients studied. A trial involving cancer patients with several different types of tumors found that Cordyceps taken over a two month period at 6 g per day, improved subjective symptoms in the majority of patients. White blood cell counts were kept high while tumor size was significantly reduced in approximately half of the patients. (Zhou et al (1998))
Mechanism Of Action For Cordycepin (see illustrations below to follow steps)
There is evidence of another mechanism at play in the Cordyceps antitumor response besides the well-known immune modulation triggered by the polysaccharide compounds. This other mechanism has to do with the structure of at least some of the altered nucleosides found in Cordyceps, exemplified by the compound cordycepin [3’deoxyadenosine]. This is a molecule almost identical to normal adenosine, with the exception that it is lacking an oxygen atom on the ribose portion of the molecule at the 3’ position. The same lack of this 3’ oxygen can be seen in other Cordyceps compounds as well, such as Dideoxyadenosine, (Didanosine™, Videx™). The lack of oxygen at this particular position is thought to be important in a very specific way. The structure of DNA depends on this oxygen to create the bond between adjacent nucleosides. This bond is between the 3’ and the 5’ positions on the ribose portions of the nucleosides, effectively forming the ‘ladder structure’ that holds the DNA together. In the replication of any cell, the first step is the separation of the DNA molecule down the middle, like unzipping, between the pairs of complimentary nucleosides. The next step is the insertion, one at a time, of new compliment nucleosides. These form hydrogen bonds between the complement pairs, and form phosphate-sugar bonds between the 3’ and 5’ position at the outside edge of the molecule, which is the ribose portion. This, in essence, is the structure that holds the DNA together. The synthesis of the new DNA molecules proceeds apace, with the sequential insertion of new compliment nucleosides one at a time into the newly forming DNA molecule, until the original strand of DNA is replicated twice, each of these strands being exact copies of the original and forming the genetic code for a new generation of cells. That is, this synthesis continues to proceed with the insertion of each new nucleoside, unless a 3’ deoxyadenosine (cordycepin) molecule is pulled in. When this happens, there is no oxygen present at that vital position to form the 3’-5’ bond, and the replication of the new DNA molecule stops. Once the DNA synthesis stops, the cell cannot continue to divide and no new cell is formed. In normal mammalian cells, this insertion of the deoxygenated adenosine is of little importance, as healthy cells have an inherent DNA repair mechanism. When this sort of error occurs, the altered nucleoside (the cordycepin) is removed from the string of nucleosides, and a new segment of adenosine is inserted. However, by their very nature, cancer cells have lost this DNA repair mechanism. (If they could correct their DNA errors, they would not be cancer cells).
Ilustration: Some of the unique nucleosides found in Cordyceps
Most bacteria and all viruses (including the HIV virus) lack this DNA repair mechanism. When we look at the rate at which cancer cells replicate, it is clear how this mechanism could exert a significant antitumor response. For example, normal healthy breast tissue cells have an average life span of about 10 days, after which the reproduce and a new cell is formed. But breast cancer cells multiply much quicker than healthy cells. They reproduce themselves on average every 20 minutes. This means that the breast cancer cells are replicating about 750 times faster than the surrounding healthy tissue. If the cordycepin were equally toxic to both types of cells, it would be killing off the cancer cells 750 times faster than the healthy cells. But because of that DNA repair mechanism in the healthy cells, cordycepin appears not to interfere with the healthy cell replication, and the tumor-cell kill rate is actually much higher than the 750-to-1 ratio. The same sort of DNA interruption mechanism is responsible for the antitumor effects of some other chemotherapy agents as well. This same mechanism of DNA synthesis inhibition is probably the responsible mechanism for the anti-viral effects seen with cordycepin as well. See the following illustrations for a structural analysis of this mechanism. (Holliday 2004b) (Liu and Zheng, 1993 and others by inference)
Ilustrations:
Purpose of this published study is scientific information and education, it should not be used for diagnosing or treating a health problem or disease. This website is designed for general education and information purposes only and does not substitute for professional medical advice, examination, diagnosis or treatment.
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