WHAT DOES CURRENT RESEARCH TELL US ABOUT THE ROLE MUSHROOMS PLAY IN FIGHTING CANCER?
Just like an old soda can that is melted and reformed into a new can, the cells in our body are frequently recycled and replaced. Every few days, cells are consumed by specialized white blood cells, stripped of their components, and used to form new and healthier cells. The recycling of cells is known as apoptosis, and when this system is not functioning properly, major problems can arise. If cells are produced faster than they are consumed, the result can be the growth of cancerous tumors. A well-equipped immune system maintains apoptosis and keeps cancerous cells from growing.
Our immune systems are like little galaxies where interplanetary warfare is occurring. Defense cells such as natural killer cells and macrophages search the body for mutated cancerous cells and induce apoptosis to destroy what they find. Intricate receptors recognize potentially dangerous cells and send electrical signals to relay the message throughout the immune system. Enzymes become activated and catalyze the production of billions of defense cells that are capable of eradicating cancerous cells from the body. Large populations of defense cells insure that mutated cells are destroyed before they pose a real threat to our system. Fortunately, a healthy diet can contribute to the proliferation of defense cells so that cancer never has a chance to spread.
Mushrooms have been at the center of anti-cancer research due to their apparent effect on the immune system. According to a review published in the Journal of Cellular Microbiology, mushrooms contain a group of polysaccharides–long chains of sugars–known as beta-glucans that enhance the body’s defense mechanisms, including apoptosis. Researchers at the Institute of Infectious Disease and Molecular Medicine have shown that beta-glucans from a variety of mushrooms bind to four different pattern recognition receptors. Like a key that fits into a lock, each receptor accepts only a unique set of beta-glucans. Once a beta-glucan molecule is bonded to a receptor, the associated pathway is activated. A recent article published by researchers at Bastyr University and University of Minnesota showed the beta-glucan polysaccharide-krestin (PSK), found in turkey tail and reishi mushrooms, binds to the TLR4 receptor and activates a pathway that leads to the secretion of a proteinaceous molecule that literally melts the membrane of cancerous cells. Scientists from the Department of Biofunctional Chemistry at Kobe University in Japan discovered that a beta-glucan derived from shiitake mushrooms has a similar anti-tumor effect to that of PSK. And a study published by the Journal of Leukocyte Biology in 2012 demonstrated that the receptor Dectin-1, when bonded to fungal beta-glucans, releases a white blood cell growth factor that triggers the production of a whole host of defense cells. The research on how different beta-glucans activate important immunological pathways suggests that eating a variety of mushroom species can boost immune response against cancerous cells.
While the research mentioned previously focused on how certain beta-glucans affected specific pathways, experiments have also been conducted to test the broad effect of mushrooms on cancer growth, prevention, and radiation treatment. The Journal of Immunopharmacology and Immunotoxicology published data from an experiment conducted in 1997 in which mice were fed a potent carcinogen and some were supplemented with mushrooms. Bladder carcinoma was decreased by half in mice supplemented with oyster, shiitake, or maitake mushrooms. A study published 2006 in the Journal of Bioscience, Biotechnology, and Biochemistry, demonstrated that Reishi mushroom extract significantly increased the life span of mice that had been implanted with tumors. More studies have been conducted, and each concludes the consumption of mushrooms maintains healthy levels of defense cells and increases immunological activity. While the medicinal properties of mushrooms have not been confirmed by the FDA, data from top research institutions and journals suggest that consuming edible mushrooms may significantly decrease cancerous growth and increase lifespan in cancer patients.
Beta-Glucans: Long chains of glucose (sugar) units with a specific bond orientation. Beta-glucans range in molecular weight and length and have different branch points. Depending on their characteristics, they have varying effects on the immune system. Humans cannot synthesize beta-glucans.
Cytokines: Are immunomodulating proteins; they send signals, and allow cells in the immune system to communicate and carry out tasks in response to information.
Dectin-1: A major pattern recognition receptor for beta-glucans on macrophages, neutropils, and dendritic cells. When Dectin-1 binds to beta-glucans, it directly induces GM-CSF cytokine production. GM-CSF is a growth factor that influences the production of a number of white blood cells. GM-CSF is currently used as a medication to increase white blood cell populations following chemotherapy and has recently been evaluated as a component in HIV medication.
Dendritic Cells: Cells that collect and transfer information to other defense cells. When an antigen is detected by dendritic cells, they pass the information on to other cells that will then build immunity and respond accordingly.
Enzymes: Proteins that catalyze reactions by lowering the amount of energy needed for a reaction to occur. If the reactions that take place in our bodies were to be repeated in the laboratory without the use of enzymes, many of them would require extremely high heat (energy). Enzymes are very efficient, produce no waste, and keep us alive.
Macrophages: Are cells that engulf and digest pathogens, cancerous cells, and debris. Macrophages have receptors that bind to proteins and carbohydrates, and they can transmit information received by these receptors to influence the production of cytokines.
Natural Killer Cells: Are defense cells that can recognize dangerous cells, mark and destroy them, and relay information to other cells. Most defense cells require activation, but natural killer cells can recognize dangerous and stressed cells and kill them without receiving a message to do so from another cell. Natural killer cells provide quick response against pathogens and cancerous cells.
Neutrophils: Are the most common white blood cell. They respond to cellular signals from injuries, inflammation, and cancer. Neutrophils are similar to macrophages in that they consume damaged cells.
Pattern Recognition Receptor: Are proteins that bind to specific structures and activate pathways after bonding. Many pattern recognition receptors bond to carbohydrates found in the cell walls of pathogens, which may explain why the beta-glucans in mushrooms stimulate an immune response.
Polysaccharide-Krestin (PSK): Is a beta-glucan bonded to a protein. PSK has been shown to enhance apoptotic cell death when used in conjunction with other anti-cancer drugs such as doxorubicin. Patients undergoing chemotherapy have had increased rates of survival when taking PSK.
TLR4 Receptor: Is a pattern recognition receptor that binds to polysaccharide-krestin from turkey tail and reishi mushrooms. It induces the secretion tumor necrosis factor-alpha, which leads to apoptotic cell death.
White Blood Cell Growth Factor: Stimulates the production of a myriad of defense cells. The cytokine GM-CSF is the white blood cell growth factor that is released when Dectin-1 is activated.
Selected Research and Highlights:
Brown, G., & Gordon, S. (2005). Immune recognition of fungal β-glucans. Cellular Microbiology, 7(4), 471-479.
“β-glucans are emerging as a major target for the recognition of fungal pathogens. A number of receptors for these carbohydrates have been identified, which upon recognition, trigger a variety of immune responses.”
“The administration of purified β-glucans has been shown to have a number of beneficial effects, including protection against tumour development and infections with fungal, bacterial, viral and protozoal pathogens, prompting interest in the pharmaceutical development of these carbohydrates.”
Tsoni, S. V., & Brown, G. D. (2008). β-glucans and dectin-1. Annals of the New York Academy of Sciences, 1143(1), 45-60.
“Four PRRs for these carbohydrates have been identified, including scavenger receptors, complement receptor 3 (CR3), lactosylceramide, and more recently, dectin-1.”
“β-glucans are potent immunomodulators with many potential applications.”
Price, L. A., Wenner, C. A., Sloper, D. T., Slaton, J. W., & Novack, J. P. (2010). Role for toll-like receptor 4 in TNF-alpha secretion by murine macrophages in response to polysaccharide krestin, A Trametes versicolor mushroom extract. Fitoterapia, 81(7), 914-919.
“Polysaccharides can activate immune responses by enhancing the secretion of TNF-alpha, IL-6 and other inflammatory cytokines. Pathogen recognition receptors also serve to bind ligands that prime immune responses. These immune modulating responses are of particular interest in cancer prevention and treatment research.”
Okamoto, T., Kodoi, R., Nonaka, Y., Fukuda, I., Hashimoto, T., Kanazawa, K., et al. (2004). Lentinan from shiitake mushroom (Lentinus edodes) suppresses expression of cytochrome P450 1A subfamily in the mouse liver. Biofactors, 21(1-4), 407-409.
“Mushroom polysaccharides, especially β-glucans such as lentinan from Lentinus edodes, possess the anti-tumor and immunomodulating activities through the cytokine production from immunocytes.”
Masuda, Y., Togo, T., Mizuno, S., Konishi, M., & Nanba, H. (2012). Soluble β-glucan from Grifola frondosa induces proliferation and Dectin-1/Syk signaling in resident macrophages via the GM-CSF autocrine pathway. Journal of leukocyte biology, 91(4), 547-556.
“β-Glucan, a major component of the fungal cell wall, is generally recognized by PRRs expressed on macrophages and DCs, such as Dectin-1.”
“This is the first study to demonstrate that purified β-glucans, such as MD-Fraction and curdlan, induce GM-CSF production directly, resulting in Dectin-1/Syk activation in resident macrophages. In conclusion, we demonstrated that MD-Fraction induces cell proliferation and cytokine production without excessive inflammation in resident macrophages, supporting its immunotherapeutic potential.”
Kurashige, S., Akuzawa, Y., & Endo, F. (1997). Effects of Lentinus edodes, Grifola frondosa and Pleurotus ostreatus administration on cancer outbreak, and activities of macrophages and lymphocytes in mice treated with a carcinogen, N-butyl-N-butanolnitrosoamine. Immunopharmacology and Immunotoxicology, 19(2), 175-183.
“Mice were treated with a carcinogen every day for 8 weeks and some were supplemented with shitake, oyster, and maitake. 100% treated with the carcinogen developed bladder carcinoma. 52.9% with shitake, 46.7 with Maitake, and 65% with oyster. Chemotactic activity of macrophages was suppressed in mice treated with the carcinogen alone, but maintained at an almost normal level when treated with the mushrooms. Lymphocytes collected showed almost normal blastogenic response with the mushrooms but almost completely retarded their response. Cytotoxic activity of lymphocytes normal with mushrooms and significant depression of Natural Killer cell activity without mushrooms.”
Nonaka, Y., Shibata, H., Nakai, M., Kurihara, H., Ishibashi, H., Kiso, Y., et al. (2006). Anti-tumor activities of the antlered form of Ganoderma lucidum in allogeneic and syngeneic tumor-bearing mice. Bioscience, Biotechnology, and Biochemistry, 70(9), 2028-2034.
“We investigated the anti-tumor effects of a dry powder preparation of the antlered form of Ganoderma lucidum (G. lucidum AF, rokkaku-reishi in Japanese), a variant type of G. lucidum, not only in allogeneic Sarcoma 180-bearing ddY mice, but also in syngeneic MM 46-bearing C3H/He mice. G. lucidum AF inhibited tumor growth and elongated the life span when orally administered to mice by free-feeding of a 2.5% G. lucidum AF-containing diet. It also showed anti-tumor activity in spite of post-feeding after tumor inoculation. G. lucidum AF significantly countered the depression of splenic CD8+ cells and protected the decrease in interferon-gamma (IFN-gamma) production in regional lymph nodes of MM 46-bearing mice, indicating that the anti-tumor activity of G. lucidum AF might be caused by its immunostimulating action. These results suggest that the ingestion of G. lucidum AF can be useful for the prevention and curing of cancer.”
Furusawa, E., Chou, S. C., Furusawa, S., Hirazumi, A., & Dang, Y. (1992). Antitumour activity of Ganoderma lucidum, an edible mushroom, on intraperitoneally implanted Lewis lung carcinoma in synergenic mice. Phytotherapy Research, 6(6), 300-304.
“An aqueous extract of Ling-Zhi [Reishi] significantly increased the life span of tumour-implanted mice, when administered intraperitoneally alone or in combination with cytotoxic antitumour drugs.”
 Brown, G., & Gordon, S. (2005). Immune recognition of fungal β-glucans. Cellular Microbiology, 7(4), 471-479.
 Tsoni, S. V., & Brown, G. D. (2008). β-glucans and dectin-1. Annals of the New York Academy of Sciences, 1143(1), 45-60.
 Price, L. A., Wenner, C. A., Sloper, D. T., Slaton, J. W., & Novack, J. P. (2010). Role for toll-like receptor 4 in TNF-alpha secretion by murine macrophages in response to polysaccharide krestin, A Trametes versicolor mushroom extract. Fitoterapia, 81(7), 914-919.
 Okamoto, T., Kodoi, R., Nonaka, Y., Fukuda, I., Hashimoto, T., Kanazawa, K., et al. (2004). Lentinan from shiitake mushroom (Lentinus edodes) suppresses expression of cytochrome P450 1A subfamily in the mouse liver. Biofactors, 21(1-4), 407-409.
 Masuda, Y., Togo, T., Mizuno, S., Konishi, M., & Nanba, H. (2012). Soluble β-glucan from Grifola frondosa induces proliferation and Dectin-1/Syk signaling in resident macrophages via the GM-CSF autocrine pathway. Journal of leukocyte biology, 91(4), 547-556.
 Kurashige, S., Akuzawa, Y., & Endo, F. (1997). Effects of Lentinus edodes, Grifola frondosa and Pleurotus ostreatus administration on cancer outbreak, and activities of macrophages and lymphocytes in mice treated with a carcinogen, N-butyl-N-butanolnitrosoamine. Immunopharmacology and Immunotoxicology, 19(2), 175-183.
 Nonaka, Y., Shibata, H., Nakai, M., Kurihara, H., Ishibashi, H., Kiso, Y., et al. (2006). Anti-tumor activities of the antlered form of Ganoderma lucidum in allogeneic and syngeneic tumor-bearing mice. Bioscience, Biotechnology, and Biochemistry, 70(9), 2028-2034.