Medicinal Mushrooms Fight Cancer: Mechanisms

Medicinal Mushrooms Fight Cancer: Mechanisms

How Medicinal Mushrooms Fight Cancer: An Introduction to the Mechanisms

The Overview of Mechanisms

The activity of medicinally active compounds from mushrooms is very complex and diverse. The most important medicinal mushroom mechanisms are stimulation of the host mediated immune response (immunomodulation) and cytotoxic/cytostatic effects.

Both inhibit the 8 main stages of carcinogenesis:

  • chronic inflammation (may induce mutations and adaptations leading to cancer)
  • cancer cell proliferation (uncontrolled cell division and growth)
  • adhesion (ability to adhere to each other and healthy cells)
  • apoptosis (cancer cells have lost the ability for programmed cell death)
  • angiogenesis (building new blood vessels that feed the tumor)
  • gene expression (using the information from a gene to synthesize a gene product, such as a protein or functional RNA)
  • invasiveness (cancer cells invade and spread through healthy tissue)
  • metastasis (spread to distant organs).

Mediating the host’s immune system, commonly called “boosting the immune system”, refers to the various ways of stimulating and modulating the general and cancer-specific host-mediated immune response, both innate and acquired. Fungal beta glucans, notably, influence these mechanisms.

Cytotoxicity, or toxicity to cancer cells, is a direct effect leading to cancer cell death by necrosis or apoptosis (programmed cell death). This includes carcinostatic modifications (slowdown of proliferation, or uncontrolled cancer cell division), faster maturation into differentiated benign cells, and modifying the cancer cells so the immune system can easily recognize them.

Agarikon.1 component strongly inhibits squamous cell carcinoma.
Effects of Agarikon.1 on squamous cell carcinoma in vitro.
Left is the control; on the right a 50% concentration of a single Agarikon.1 component demonstrating a direct cytotoxic effect (killing cancer cells).
Source: Rudjer Boskovic Institute

Modifications of Host Mediated Immune Response

Some medicinal mushroom compounds (notably some beta glucans) improve the host-mediated cancer immune response. When users consume beta glucans, they stimulate the Peyer’s patches in the intestinal walls. Peyer’s patches help generate the immune response with macrophages, dendritic cells, B- and T-lymphocytes. The body adapts by boosting the immune system.

peyer's patch diagram
Peyer’s patches, mucosal tissues located in the small intestine, help generate the immune response with macrophages, dendritic cells, B- and T-lymphocytes. Beta glucans, like lentinan from Lentinus edodes (shiitake), act like antigens and stimulate the immune response.

Lentinan, a compound from shiitake and an official anticancer drug in Japan, is a good example how most beta glucans work. While not toxic to cancer cells, lentinan modulates the immune system so it is more aggressive and efficient against them. Lentinan improves the production of:

  • immune-strengthening substances:
    • antibodies
    • cytokines (interferons and interleukins, esp. IL-1)

and strengthens the activity of:

  • natural killer cells (NK cells)
  • cytotoxic macrophages
  • cytotoxic and helper T-lymphocytes
  • classical and alternative complement pathways

and inhibits the creation of substances that weaken immunity (immunosuppressive).

Flow chart of Lentinan antitumor activity
Antitumor mechanisms of lentinan (Chihara, 1981). Lentinan, a mushroom specific beta glucan, is just one of thousands of active compounds of Lentinus edodes (shiitake); but it activates multiple pathways that lead to tumor cell destruction.

As you can see, the activity of lentinan is well-known: it is also very complex. Lentinan blocks various pathways important for cancer progression.

Basic molecular structure of lentinan, high molecular weight polysaccharide from Lentinus edodes (shiitake). This structure is repeated many times, the molecular weight of lentinan is about 500,000 Da. Lentinan has been proven to boost the immune system, fight cancer and viral infections.
Basic molecular structure of lentinan, beta glucan from Lentinus edodes (shiitake). This structure repeats itself many times; the molecular weight of lentinan is about 500,000 Da. 
Lentinan has been proven to boost the immune system, fight cancer and viral infections.

Other beta glucans (e.g. SPG, PSK …) from medicinal mushrooms work similarly, but not the same. Some mainly

  • stimulate the innate and acquired immunity responses
  • enhance the production of immunocompetent cells
  • increase their functional abilities
  • help them recognize and kill cancerous cells
  • protect the immune system from weakening, etc.

Cytotoxic and Carcinostatic Activity

There are many medicinal mushroom compounds (certain polysaccharides, protein-bound polysaccharides, lignins, triterpenes, purines, polyphenols…) that do not only modify the immune system. Some of them are toxic to cancer cells (cytotoxicity), and others subtly change their functioning.

Many medicinal mushroom compounds exhibit direct cytotoxic activity. They can cause cancer cell death by inducing necrosis and promoting apoptosis. Necrosis is a cell injury that leads to cell death: the compounds damage cancer cell membranes and mitochondria (the “power plant” of cells). Apoptosis is a programmed cell death: the compounds trigger those biochemical events that lead to cell death (one of the properties of cancer cells is that they lose this ability, allowing for proliferation, or uncontrolled cell division).

But there are more insidious processes that detrimentally modify cancer cell functions: they inhibit cancer cell development or speed up their maturation (turning them into benign, differentiated cells), make them more easily detectable and vulnerable to the immune system, etc.

apoptosis mechanism (signal transduction pathways) diagram
Like most cell processes, cell apoptosis is quite complex. The initiation of cell apoptosis is triggered by Tumor Necrosis Factor (TNF) receptor family and extrinsic signals.

And while we know a lot about the mechanisms, there are still many unresolved issues.
The research of mechanisms continues, but we already know without any doubt that medicinal mushroom compounds can help cancer patients:

  • improve overall outcome (including chance of survival and longer life span)
  • help switch progressive tumor disease to stable disease
  • reduce cancer size in primary tumors and metastasis
  • endure chemotherapy and radiotherapy, with less side effects
  • tolerate surgery better and accelerate post-operative recovery by improving wound healing, etc.
  • prevent immune system weakening due to official cancer therapy
  • greatly increase the quality of life (more strength and endurance, better sleep and appetite; less pain, nausea and fatigue).

The research of mechanisms explains these effects, which, paradoxically, were first observed in human clinical trials – and also reported in cohort studies that Myko San has completed.