Mushrooms and the Research in Cancer

Mushrooms are jam-packed superfoods that have been used in culinary and medicinal preparations for thousands of years. They are full of nutrients including proteins made of amino acids, fibres, carbohydrates—including polysaccharides (β‑glucans), vitamins (B2, B3, folate/B9, B12, C, D2, and E), and minerals (K, P, Mg, Ca, Cu, Fe, and Zn). They also include many bioactive substances such as phenolic compounds, glycosides, alkaloids, volatile oils, terpenoids, flavonoids, lectins, enzymes, and organic acids. ¹ Mushrooms are being studied extensively and are best known for properties such as antioxidant, anticancer, antidiabetic, antiallergic, immunomodulating, cardiovascular protector, cholesterol-improving, antimicrobial, detoxification, and hepatoprotective effects. ^{2, 3, 4, 5, 6}

This article will focus on the potential use of mushroom extracts in cancer and the protective and synergistic effects mushrooms can have on chemotherapy and radiation treatments. Please note that this information is for informational purposes only and should not be taken as medical advice or treatment, nor should the information in this article substitute medical advice or treatment.

Cancer is one of the leading causes of death worldwide and involves a high clinical, social, and economic burden. Overall basic characteristics of cancerous tumours involve self-sufficient growth, avoidance of growth-inhibition signals, evading apoptosis, unlimited replicative potential, formation of new blood vessels (angiogenesis), and tissue invasion and metastasis. ⁷ Standard treatments such as chemotherapy are associated with toxicity towards normal cells and tissues, often deplete the immune system, and come with undesirable side effects. A serious detrimental effect of chemotherapy is bone-marrow suppression or myelosuppression, which causes neutropenia, and in turn stalls treatment before full therapeutic effects can be achieved.

Many mushrooms have immune-stimulating action that may protect against the myelosuppression of chemotherapy, potentially allowing for better outcomes. ⁸ Medicinal mushrooms can also counteract side effects of chemotherapeutics such as nausea, malaise, fatigue, and anemia. Some preliminary findings suggest that mushrooms given with standard anticancer drugs may increase the effect of these therapies, which may be an important consideration in cancers resistant to chemotherapeutics.

The active constituents in mushrooms with the most research backing are polysaccharides and triterpenoids. The polysaccharides, which include β‑glucans, have demonstrated antitumour, immunomodulation, and antioxidant properties in vitro. ^10,11 Triterpenoids are also strong antioxidants and have shown abilities to inhibit cancer-cell proliferation and metastasis in vitro. ¹²

Mushrooms exert their immunomodulating effects by affecting cytokine pathways. First, a little bit about the immune-response patterns. The TH1 pattern produces cytokines such as IFN‑γ, IL‑12, and TNF‑α, which stimulate an immune response to fight cancer cells. IFN‑γ enhances natural killer cells and macrophages to destroy tumours and pathogens. On the contrary, a TH2 pattern, often associated with allergies and asthma, secretes IL‑4 which can decrease production of IFN‑γ, thus inhibiting the immune response to cancer.¹³

Many of the side effects of chemotherapy and radiation—including fatigue, anxiety, and malaise—can be attributed to increases in proinflammatory cytokines (IL‑1, IL‑6, and TNF‑α). In theory and based on the in vitro research on the effects of mushrooms on the immune responses, mushrooms that can promote the TH1 immune pattern and decrease inflammation due to TH2 response, creating a positive immune response against cancer. Mushrooms, therefore, may play an important role in limiting side effects of standard treatment protocols by decreasing inflammation, and further evidence in human studies is required and ongoing.

Reishi (Ganoderma lucidum)

Known as the “king of mushrooms,” reishi has been demonstrated in preclinical studies to decrease viability of cancer cells, induce apoptosis, and inhibit cell proliferation. ¹⁴ Taken at the appropriate dose, reishi does not produce any major toxicity or side effects. ¹⁵ With the ability to now break open the wall of mushroom spores, preclinical research is underway to determine their effects on immune-system cells. ¹⁶ Spores are the reproductive cells of a fungus, which are ejected from the cap when the fruiting bodies are mature. Just like the fruiting bodies, spores contain polysaccharides that stimulate the immune system, as well as triterpenoids that may inhibit cell proliferation in cancer. In a preclinical, in vitro study, extracts using the sporoderm-broken spores (SBSGL) and fruiting bodies of reishi show potential as chemosensitizers when given in combination with taxane drugs. ¹⁷ Another in vitro study compared SBSGL with cisplatin treatment alone. The combination of cisplatin with SBSGL appeared to have enhanced the decrease in volume and weight of tumours. ¹⁸ Triterpenoids extracted from reishi include ganoderic acids. Ganoderic acid D (GA‑D) extracted from SBSGL is highly oxygenated and can have potentially antitumour effects by inducing apoptosis. ¹⁹ Ganoderic acid T (GA‑T) has demonstrated the inhibition of tumour invasion, cell adhesion, and metastasis in human colon-cancer cell lines. ²⁰ Mechanistically, preliminary findings suggest that ganoderic acid A (GA‑A) may also help to increase the amount of cisplatin inside tumour cells, promoting apoptosis. ²¹ Other ganoderic acids (GA‑Mf, GA‑S, GA‑Me) have been shown to induce apoptosis in cancer cells via mitochondrial dysfunction. ²² Overall, the triterpenoids and polysaccharides from reishi have potential to be useful for human health, based on the extensive preclinical data demonstrating mechanisms that will hopefully be studied in clinical research.

Turkey Tail (Trametes versicolor or Coriolus versicolor)

Studies investigating leukemia, lymphoma, and gastric and lung cancers show that cancer-cell lines can be markedly inhibited in vitro by extracts from Trametes mushrooms. ²³ Two proteoglycan polysaccharides found in Trametes, krestin (PSK) and polysaccharide peptide (PSP), have been investigated in human clinical breast-cancer studies for their anticancer and immunomodulatory activities. ²⁴ Used in adjunctive treatment plans with chemotherapy, groups receiving PSK had better outcome measures, likely due to its immunomodulation ability. ²⁵ It was also shown that PSK and trastuzumab (a drug often given in metastatic breast cancer and sometimes stomach cancers), when used separately, inhibited tumour growth at similar rates. Given together, they could reduce the growth of tumours by 96%. ²⁶ The Trametes extract, PSK, also increased the efficacy of docetaxel (a drug used to treat gastric cancer): PSK allowed the use of a lower dose of docetaxel to produce the same level of apoptosis. ²⁷ In a randomized, controlled study with colorectal cancer patients, the 5‑year survival rate was assessed. ²⁸ PSK was given at 3 g/d for two years in conjunction with standard therapy versus a control (presumedly standard therapy alone). ^29,30 Compared to the control group, the PSK group showed a statistically significant (p = 0.038) increase in survival rate of 86.8% compared to 60%.³¹

In tumour-bearing mice given extracts of Trametes, a remarkable immune effect was seen with increases in positive cytokine patterns, specifically TNF‑α; IFN‑γ; and IL‑2, ‑6, and ‑12. ³² PSP, a β‑glucan from Trametes mushrooms, additionally modified the gut microbiome. ³³ Extracts from Trametes show clinical evidence as an adjunctive support in certain cancers, and overall, improved immunity.³⁴

Maitake (Grifola frondosa)

Grifola mushroom is rich in proteoglycans, which have immune-stimulatory abilities. Preclinical studies have demonstrated that the MD‑fraction β‑glucan extracted from Grifola helped to prevent the myelosuppression and nephrotoxicity induced by cisplatin. Given at 8 mg/kg/d in a mouse model treated with cisplatin, the mice did not experience a decrease in NK cells, dendritic cells, or macrophages. ³⁵ Grifola also inhibited hepatocellular carcinoma, reducing proliferation, inducing the cell-cycle arrest, and promoting apoptosis in vitro. ³⁶ In another mouse model of breast cancer, there was a reduction in the migration and invasion of mammary tumour cells, resulting in a less aggressive cancer. ³⁷

And More…

Other mushrooms of interest include Chaga (Inonotus obliquus), which shows strong antioxidant activity likely due to high phenolic content.

It also exhibits anticancer action via antiproliferation and apoptosis in colorectal cancer cell lines. ³⁸ Lion’s mane (Hericium erinaceus) may induce NK activity, the action of macrophages, and inhibition of angiogenesis contributing to antitumour and immunomodulatory effects. ³⁹ Another beneficial mushroom, button mushroom or portobello (Agaricus bisporus), is one commonly eaten. An extract of this mushroom high in β‑glucans was shown to increase the effectiveness of doxorubicin, by increasing the amount of this drug in liver cancer cells and therefore promoting apoptosis in vitro. ^40,41

Immunomodulation is an important and broad-spectrum therapeutic consideration in patients undergoing cancer treatment. Science is observing and investigating the mushroom’s therapeutic compounds, including β‑glucans, and their immunomodulation effects. Additionally, mushrooms are a great source of prebiotics, which can positively modify the microbiome. A healthy microbiome may also help to benefit the immune system and to regulate inflammation, which may be at the root of many degenerative disease states, such as cancer. Mushrooms contain so many chemical components and have the potential to regulate multiple processes simultaneously. ⁴³

Much of the research has been in vitro or in mice; all show promising effects, but there is a need for more human clinical trials. Many studies are very recently published, and many are ongoing, so it will be interesting to see the evolution and potential of mushrooms’ use in the future.