Mushroom polysaccharides as anticancer agents-Dr C R Meera
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Mushrooms are a repertoire of biologically active compounds. They were part of human diet and culture since ancient history. They have many significant pharmacological properties. Mushroom polysaccharides are the most potent mushroom-derived compounds. Mushroom polysaccharides are used as anticancer drugs, and play an important role in immunotherapy and cancer adjuvant therapy.
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Mushroom polysaccharides as anticancer agents-Dr C R Meera
- 1. Mushroom polysaccharides as Anticancer Agents By Dr. C R Meera, M Sc., Ph.D, Assistant Professor & Head Department of Microbiology St Mary’s College, Thrissur-680020, Kerala St Mary’s College Thrissur
- 2. St Mary’s College Thrissur Part I - Mushrooms- An Introduction
- 3. St Mary’s College Thrissur Mushrooms- An Introduction • Mushrooms have been consumed since the earliest history • Romans perceived them as the “Food of the Gods.” • Ancient Greeks believed mushrooms a “strength source for warriors” in battle • Chinese culture has treasured mushrooms as a health food, an “elixir of life” • Mushrooms to fight cancer is known for a long time in Korea, China, Japan, Russia, USA, and Canada. Image courtesy: en.wikipedia.org
- 4. • Any of the fleshy fruiting bodies of fungi typically produced above ground on soil or on their food sources • The term ‘mushroom’ was defined by Chang and Miles (1992) as ‘a macrofungus with a distinctive fruiting body, which can be either hypogeous or epigeous, large enough to be seen with the naked eye and to be picked by hand’ Image courtesy: en.wiktionary.org
- 5. • Kingdom- Fungi • Phylum- Basidiomycota • Class- Basidiomycetes and Ascomycetes • Mushrooms are also called “Macromycetes” • The number of mushroom species on earth is estimated to be 140 000, only 10% are identified and explored. • Mushrooms represent a major and yet largely untapped source of powerful new pharmaceutical products Image courtesy: bbcearth.com
- 7. Image courtesy: kids.wng.org Image courtesy: realmushrooms.com Mushrooms releasing spores
- 8. Mushroom- Life Cycle Image courtesy: sciencelearn.org.nz
- 9. Mushroom Development Stages Image courtesy: tinyplantation.com
- 10. Mushrooms-Classification Edible Mushrooms Non-edible Mushrooms Medicinal Mushrooms Toxic Mushrooms
- 11. Edible Mushrooms • Mushrooms are considered “nutraceutical foods” - a delicacy with high nutritional and functional value. • Nutrional value- reasonable amounts of proteins, carbohydrates, minerals, fibres and vitamins (B1, B2, B12, C, D, and E). • Meat of Vegetable world- Low in calories, sodium, fats, and no cholesterol • Agaricus bisporus - Button Mushroom (Most widely cultivated) • Lentinus edodes - Shiitake mushroom • Pleurotus spp - Oyster mushroom • Calocybe indica - Milky mushroom • Volverialla spp - Paddy straw mushroom • Flammulina velutipes - Winter mushroom
- 12. Button Mushroom (Agaricus bisporus) Shiitake Mushroom (Lentinus edodes) Edible Mushrooms
- 13. Oyster Mushroom (Pleurotus spp) Edible Mushrooms Milky Mushroom (Calocybe indica)
- 14. Paddy straw Mushroom (Volverialla spp) Winter Mushroom (Flammulina velutipes) Edible Mushrooms
- 15. Non-Edible Medicinal Mushrooms • Pharmacologically important primary and secondary metabolites • Primary metabolites – Polysaccharides, Polysaccharide-protein complexes, proteins and lipids • Secondary metabolites - triterpenes, steroids, anthraquinones, benzoic acid derivatives, quinolones, phenols, etc • Ganoderma spp., - Reishi • Phellinus spp., - Bracket fungus
- 16. Ganoderma spp Phellinus spp Non-Edible Medicinal Mushrooms
- 17. Toxic Mushrooms • Commonly called “Toadstool” • Toxic mushrooms produce harmful chemicals (1)Protoplasmic poisons- generalized destruction of cells, followed by organ failure (2)Neurotoxins- neurological symptoms such as profuse sweating, coma, convulsions, hallucinations, excitement, depression etc (3)Gastrointestinal irritants - rapid, transient nausea, vomiting, abdominal cramping and diarrhoea (4)Disulfiram-like toxins- toxic if alcohol consumed with in 72 hrs
- 18. Toxic Mushrooms Amanita spp.- Death Angel or Death cap Psilocybe spp.- Magic Mushroom or Gold cap
- 19. St Mary’s College Thrissur Part II-Medicinal Properties of Mushrooms
- 20. Medicinal Properties of Mushrooms Anti-diabetic Reduce Cholesterol Reduce Hypertension Anti-aging Weight management Antimicrobial To treat Anaemia Hepato/Cardio protective
- 21. Medicinal Properties of Mushrooms Antioxidant activity Anti-tumor Property Prevention of neurodegenerative diseases Anti-inflammatory activity Immuno- modulatory Cancer adjuvant therapy Anti-cancer Property
- 22. Anticancer Drugs from Mushrooms
- 23. Anticancer Drugs from Mushrooms Compound Origin Molecular structure Lentinan (Stomach, colorectal, and breast cancers ) Lentinus edodes 1,6-Monoglucosyl branched 1,3-β-D-glucan Image courtesy: promopharma.com
- 24. Anticancer Drugs from Mushrooms Compound Origin Molecular structure Schizophyllan (Gastric and cervical cancer/ Radiation Adjuvant Therapy) Schizophyllum commune 1,6-Monoglucosyl branched 1,3-β-D-glucan
- 25. Compound Origin Molecular structure Active Hexose Correlated Compounds (AHCC) A proprietary extract from several species of basidiomycete mushrooms, including Lentinus edodes 1,3-α-D-glucan (Pancreatic, lung, and colorectal cancers; BRM) Image courtesy: amazon.com Anticancer Drugs from Mushrooms
- 26. Anticancer Drugs from Mushrooms Compound Origin Molecular structure Maitake D-fraction Grifola frondosa 1,6-Monoglucosyl branched 1,3-β-D-glucan (BRM-Enhance the efficacy of Cisplatin) Image courtesy: evitamins.com
- 27. Anticancer Drugs from Mushrooms Compound Origin Molecular structure Polysaccharide Krestin (PSK) Coriolus versicolor 1,3 and 1,6-monoglucosylbranched 1,4-β-D glucan with binding To aspartic, glutamic, and other acidic amino acids Polysaccharide Protein (PSP) Coriolus versicolor Resemble to PSK structure but is richer in glutamic and aspartic acids CMI activation & Effective against many types of cancers- sarcoma, myeloma, mammary, colon, lung cancer, prostate cancer, etc.
- 28. St Mary’s College Thrissur Take Home Message • Mushrooms are Nature’s hidden treasure for promoting human health and quality of life. • The pharmacological potential of Mushrooms are fascinating and promising • Make mushrooms a part of your diet • It is a preventive measure to numerous devastating diseases and a perfect way to stay healthy
Editor's Notes
- Mushrooms have been part of human culture and diet since ancient history. It was also widely used in folk medicine. Romans-Food of the Gods- incredible health benefits on their consumption Ancient Greeks- a “strength source for warriors”. They fed their warriors with mushrooms for their enormous strength and stamina on battlefields. Chinese culture has treasured mushrooms as a health food, an “elixir of life”- essence or extract that can cure all diseases Means humans were very much aware of the health benefits of consuming mushrooms since ancient history and they have been used to fight cancer for a long time in Korea, China, Japan, Russia, the USA, and Canada
- As we all know mushrooms come under fungi. Fungi are eukaryotic heterotrophs that act as primary decomposers involved in biogeochemical cycles. Mushrooms are macrofungi that can grow on a variety of substrates including dead trees or in animal dung, leaf mulch, soil, and on the dead and decaying organic matter. They can be easily cultivated on various agrowastes like sawdust, straw, wood chips, logs, coffee grounds, etc. Usually, mushrooms have fleshy fruiting bodies typically produced above ground on soil or on their food sources The term ‘mushroom’ was defined by Chang and Miles (1992). According to Chang and Miles mushrooms are ‘macrofungus with a distinctive fruiting body, which can be either hypogeous or epigeous, means growing underground or above the soil. They will be also large enough to be seen with the naked eye and to be picked by hand.
- Here is the taxonomic status of mushrooms. As I have already mentioned, mushrooms come under the Kingdom- Fungi Phylum- Basidiomycota Members of mushrooms fall under Classes Basidiomycetes as well as Ascomycetes Mushrooms are also called “Macromycetes” which means macrofungi as they are fungi with large fruiting bodies The number of mushroom species on earth is estimated to be 140 000, 10% are identified and explored for their medicinal and nutritive properties Thus, Mushrooms represent a major and yet largely untapped source of powerful new pharmaceutical products
- Slide 7 & 8 A typical Mushroom consists of cap, gills, stem and volva Cap- technical term is pileus. In this figure, the umbrella like part is the cap. But the shape of the cap varies with mushrooms. It can be convex, hemispherical, bell-shaped, conical, umbonate, umbilicate, flat, or funnel-shaped. Beneath the cap we can see the gills. Gills are vertical plates radiating from the stem to the rim of the cap. But gills may also vary in their spacing and appearance in mushrooms. Gills bare the spores of the mushrooms. That’s why gills change their color. The spore-bearing gills and the gills from which spores are liberated appear in different colors. Stem: Also called stipe- a stalk-like structure of a mushroom. In many mushrooms stem and cap are distinct. But length and appearance of the stalk are different in different mushrooms. It can be long or short, thick or thin, distinct from the cap, or fused with the cap. Immature mushrooms or developing mushrooms appear as egg-shaped or oval structures consisting of mycelial buttons that are covered by a membrane called the universal veil. The membrane ruptures as the fruiting body develops from the mycelial button. Remnants of the universal veil can be seen in some mature mushrooms. It could persist as a cup of tissue around the base of the stem and is called a volva. It could be seen attached to the cap which is called a wart. Similarly in immature mushrooms, gills are covered by partial veils which also tear off as the mature cap develops in mushrooms. Remnants of a partial veil can be also seen attached to halfway of the stem. It is called the ring or skirt of mushrooms.
- Like other fungi, mushroom develops from a spore. Spore liberated from gills Billions of spores are liberated from mushroom gills. Many of them condense with water molecules to soil- germinate to form hyphae Mating of + and – stains of hyphae occur beneath the soil- hyphae feed and grow under the soil to form thick mycelial structures or hyphal knots. These immature mushroom forms are called the developing egg stage of mushrooms. Immediately after overnight rain, we can find mushroom fruiting bodies popping up from the soil as small ball-like structures called the button stage From the button stage mushrooms proceed to the fully mature fruiting bodies. In your yard there may be regions where mushrooms appear every year. Mycelia of mushrooms present underneath the soil in these regions are actually giving out mushrooms on the onset of rains Sudden change in temperature and humidity is responsible for the sprouting of mushroom fruiting bodies from the immature egg stage. So only on fruiting body development above the soil, do we notice the mushrooms. But their mycelia have been doing the groundwork for the development of fruiting bodies at the onset of favorable conditions.
- These are the different stages of mushroom development. Mycelial knots beneath the soil form the immature developing eggs of mushrooms. This is the enlarged image of the mushroom egg stage. This egg-shaped structure is enclosed by the universal veil. Inside the universal veil, we can see the immature cap or pileus, stem, and gills covered by the partial veil. On the onset of favorable conditions, preferably a temperature of 25-270 C and humidity of 90 -95 %, the universal veil of mushroom ruptures and give out the premature button stage of mushroom which appears above the soil. Then it develops into mature mushroom fruiting bodies with well-differentiated cap, stem, and gills. Remnants of the universal veil can be seen on the mature mushroom. It can be present at the bottom of the stem which is called Volva. In some mushrooms remaining of this membrane can be seen on the cap. Remnants of partial veil can be also seen on the stem in some mushrooms. Mature fruiting bodies again release spores from the gills which will germinate in the soil and the cycle continues.
- Mushrooms are classified into edible and non-edible mushrooms. Identification of edible and non-edible mushrooms is not an easy task and can be done by experts only. Non-edible mushrooms are further divided into medicinal mushrooms and toxic mushrooms Medicinal mushrooms can not be consumed. But they contain pharmaceutically important biomolecules which can be isolated and used for the prevention and treatment of diseases. Whereas toxic mushrooms cannot be consumed. Toxins are the secondary metabolites of mushrooms. If toxic mushrooms are consumed unknowingly, it causes a condition called mushroom poisoning which causes gastrointestinal discomfort like stomach pain, diarrhea, vomiting, and sometimes can be fatal.
- Edible mushrooms are delicious and are considered nutraceuticals. This means, they have nutritional value as well as pharmaceutical properties. Consumption of edible mushrooms is of incredible health benefits. Mushrooms are rich in nutrients- They contain reasonable amounts of proteins, carbohydrates, minerals, fibers, and vitamins (B1, B2, B12, C, D, and E). Mushrooms are considered the Meat of the Vegetable world- and the major attraction is that they are low in calories, have less amount of sodium, and fats, and contain no cholesterol. Common edible mushrooms include: Agaricus bisporus - Button Mushroom (Most widely cultivated) Lentinus edodes - Shiitake mushroom Pleurotus spp - Oyster mushroom Calocybe indica - Milky mushroom Volverialla spp - Paddy straw mushroom Flammulina velutipes - Winter mushroom
- These are the images of Button mushroom and Shiitake mushroom. Button mushrooms are one of the natural food sources of Vitamin D which is necessary for bone, and teeth health, immunity, calcium, and phosphorous uptake, etc. Intake of this mushroom will reduce cancer incidence, arthritis, and many other health issues. Shiitake are grown mainly in Japan, although the United States, Canada, Singapore, and China also produce them. Less cultivated in India. They are brown in color and grow naturally on decaying hardwood trees. Shiitake contains many of the same amino acids as meat
- These are the images of oyster mushroom and milky mushroom. Both are the favorite mushrooms of mushroom growers. The cultivation of these mushrooms is simple and economical. The Pleurotus mushrooms have large fruiting bodies and resemble the shell of pearl oyster. That’s why they are known as oyster mushrooms. Calocybe is an indigenous mushroom. These mushrooms are large with long, thick fibrous stalks. They appear in summer after rainfall in the fields and road verges.
- These are the images of paddy straw and winter mushrooms The paddy straw mushrooms are true tropical mushrooms that grow well on rice paddy straw Flammulina are wood-rotting edible mushrooms growing on wood trunks. They naturally produce fruiting bodies in the winter season. Hence called winter mushrooms. That’s all about the edible mushrooms. Here I have mentioned only a few of the most popular edible mushrooms cultivated around the world.
- Coming to the non-edible mushrooms. We have already seen that nonedible mushrooms are classified as medicinal and toxic mushrooms. Nonediblele medicinal mushrooms pharmacologically important primary and secondary metabolites The Primary metabolites include biomolecules like Polysaccharides, Polysaccharide-protein complexes, proteins, and lipids Secondary metabolites include triterpenes, steroids, anthraquinones, benzoic acid derivatives, quinolones, phenols, etc. Both these primary and secondary metabolites are reported to have several pharmacological properties which we will be discussed in the following sessions. Here also I have mentioned only the most popular non-edible medicinal mushrooms found all around the world. So much research has been carried out on these mushrooms. One is Ganoderma spp., commonly known as - Reishi mushrooms And the other one is Phellinus spp., commonly known as Bracket fungus Both of them are parasitic mushrooms growing on tree trunks which will eventually destroy the tree on which it is growing.
- The first image is of the Ganoderma species. It includes around 80 different species and has been extensively researched for their biological properties. Ganoderan is the anticancer drug developed from this species. They are parasitic fungi growing on tree trunks. In Kerala, the Ganoderma applanatum species is seen growing on the coconut tree trunks. Phellinus species are called bracket fungus because of their peculiar bracket like shape. They are also parasitic mushrooms. It is from this species the most potent anticancer compounds are isolated. Phellinus rimosus is the most common species found in Kerala growing on jack fruit tree trunks. Its medicinal properties will be discussed in the following session.
- Next group under the nonedible mushrooms is toxic mushrooms Toxic mushrooms are usually very attractive Toxic mushrooms are commonly called “Toadstool” They contain several harmful chemicals. They include Protoplasmic poisons which cause generalized destruction of cells leading to organ failure Neurotoxins which cause neurological symptoms such as profuse sweating, coma, convulsions, hallucinations, excitement, depression, etc. Toxic mushrooms are reported to be used by some tribal communities in religious rituals to create hallucinations. Gastrointestinal irritants may cause rapid, transient nausea, vomiting, abdominal cramping and diarrhea Disulfiram-like toxins- these toxins are activated if alcohol is consumed within 72 hrs
- When kids are asked to draw mushrooms, they usually draw a beautiful red mushroom with white dots on its cap. Members of the Amanita species are having an attractive bright red cap with white spots. They are very poisonous mushrooms commonly called Death angels or Death caps as they can cause the death of the person who consumed them The other one is Psilocybe spp. Commonly known as - Magic Mushroom or Gold cap The active compounds in this mushroom are psilocybin and psilocin. On consumption, this mushroom causes psychedelic effects (temporary altered state of consciousness). They are hallucinogenic drugs like LSD. UN has listed psilocybin and psilocin as Schedule I drugs. In US, growing this mushroom is illegal in all states
- Moving on to Part II-Nutritional & Medicinal properties of Mushrooms
- Mushrooms are considered the repertoire of pharmacologically active biomolecules and still remain an untapped source for drug discovery. Many mushrooms are reported to have several medicinal properties. Many mushrooms are having anti-microbial activity including anti-bacterial, anti-fungal, anti-viral, and anti-protozoan activities. Mushrooms are hepato as well as cardioprotective They have antidiabetic property They can reduce cholesterol and hypertension Mushrooms aid in healthy weight management They have anti-aging property They can improve the absorption of iron and thus useful in treatment of anemia
- In this presentation we are mainly focusing on the anticancer properties of mushrooms Oxidative stress is implicated in the etiopathogenesis of a variety of human diseases like cardiac diseases, arthritis, neurodegenerative diseases, and also in cancer. Mushrooms usually contain a wide variety of free radical scavenging molecules, such as polysaccharides and polyphenols This free radical scavenging activity contributes toward its anti-cancer activity Free radicals are also responsible for neurodegenerative diseases. Being strong free radical scavengers, mushrooms can prevent neurodegenerative ailments. Inflammation is a normal defense phenomenon of our body to get rid of infections. It can be of two types. Acute and chronic. Acute inflammation lasts for a few days. Chronic inflammations last for weeks, months, or even years. Inflammation is also a predisposing factor in cancer. Hence anti-inflammatory agents can be used to prevent and cure cancer. Many mushrooms are reported to have anti-inflammatory properties which contribute to their anticancer property Mushrooms are strong immunomodulators. They can boost both our humoral and cell-mediated immune systems. They are considered as BRMs. All these properties like anti-oxidant, anti-inflammatory, and immunostimulatory activities make mushrooms strong anti-tumor and anticancer agents. Also in cancer therapy, Immunotherapy is a developing technology. Mushrooms can be effectively made used in immunotherapy of cancer patients. Conventional cancer treatments like surgery, chemotherapy and radiation therapy are inevitable in cancer treatment. But all these have several side effects as they target the fast-multiplying cells in the body of a cancer patient. All these methods weaken the immune system of the patient which is already weak due to existing cancer. QoL of the patient is adversely affected by Conventional cancer treatment methods. Now, it is proposed that mushroom-derived compounds can be used in cancer adjuvant therapy. That means, mushroom-derived drugs can be used along the conventional methods. Mushroom drugs will thus improve the quality of life of cancer patients without interfering with conventional treatment methods.
- Mushroom-derived anti-cancer drugs are already available on the market. As we have already seen, mushrooms contain various components like Polysaccharides, Polysaccharide-protein complexes, proteins, lipids, triterpenes, steroids, anthraquinones, benzoic acid derivatives, quinolones, phenols, etc Among various components, Polysaccharides and Polysaccharide-protein complexes are the most potent anticancer drugs from mushrooms 6 mushroom derived anticancer drugs are available in the market which includes Lentinan, Schizophyllan, Active Hexose Correlated Compounds (AHCC), Maitake D-fraction, Polysaccharide Krestin (PSK), Polysaccharide Protein (PSP) All these are mushroom polysaccharides, mainly Beta Glucans. Glucans are polysaccharides made up of glucose units only. These drugs are widely used in China, Japan, Russia, and Korea
- Lentinan- Lentinus edodes 1,3-β-D-glucan with 1,6-Monoglucosyl branches Very good results in prolonging the life span of patients with stomach, colorectal, and breast cancers without any toxic side effects.
- Schizophyllan- Schizophyllum commune (edible)- 1,3-β-D-glucan with 1,6-Monoglucosyl branches Effective against Gastric and cervical cancer Adjuvant therapy to reduce side effects of radiation treatment. Can be taken during radiation treatment or after. Will reduce side effects.
- Active Hexose Correlated Compounds (AHCC)- A proprietary extract from several species of basidiomycete mushrooms, including Lentinus edodes Effective against pancreatic, lung, and colorectal cancers After one month of treatment with AHCC, CD4/CD8 ratio was increased in all patients and a clear modulation of natural killer levels was also observed
- Maitake D-fraction- Grifola frondose (edible) 1,6-Monoglucosyl branched 1,3-β-D-glucan Enhance the efficacy of the most common anti-cancer agent Cisplatin by inhibiting the immunodebiliation.
- Polysaccharide Krestin (PSK) and Polysaccharopeptide (PSP) are polysaccharides isolated from the mushroom Trametes versicolor or Coriolus versicolor, commonly known as the turkey tail mushroom or cloud mushroom. Both are β-glucans with immunopotentiating and anti-tumor properties against many types of cancers Directly activate CMI Effective against Melanoma, sarcoma, myeloma, and carcinomas of mammary, colon, lung, prostate, etc.