Medicinal mushrooms as an attractive new source of natural compounds for future cancer therapy

Medicinal mushrooms have been used throughout the history of mankind for treatment of various diseases including cancer. Nowadays they have been intensively studied in order to reveal the chemical nature and mechanisms of action of their biomedical capacity. Targeted treatment of cancer, non-harmful for healthy tissues, has become a desired goal in recent decades and compounds of fungal origin provide a vast reservoir of potential innovational drugs. Here, on example of four mushrooms common for use in Asian and Far Eastern folk medicine we demonstrate the complex and multilevel nature of their anticancer potential, basing upon different groups of compounds that can simultaneously target diverse biological processes relevant for cancer treatment, focusing on targeted approaches specific to malignant tissues. We show that some aspects of fungotherapy of tumors are studied relatively well, while others are still waiting to be fully unraveled. We also pay attention to the cancer types that are especially susceptible to the fungal treatments.

CONCLUSIONS

The complex anticancer potential of medicinal mushrooms may be embodied not only through inhibition of certain cancer-specific processes or targeted activation of tumor-specific apoptosis, but also through indirect actions such as immunomodulation [95]. The polysaccharide-mediated antitumor immunomodulatory action seems to be rather common for many medicinal mushrooms and gives a major input into the therapeutic potential of at least three out of the four reviewed species, which is probably determined by similar carbohydrate composition and thus similar effects on the immune system of different mushrooms. Extrapolating these data, we can suppose that other, less studied, polysaccharide-rich mushroom species could possess similar or even superior immuno-stimulatory properties. Moreover, some of additional biological activities can be used for cancer prevention, diminishing the risk of tumorigenic conditions; to such activities we can attribute antioxidant, antibacterial and anti-inflammatory properties. That is why research on whole fungal extracts (sometimes reaching to the clinical trials) and even on extracts of complex mixtures of different medicinal mushrooms [96] are the important part of the given research field.

The four mushrooms reviewed in this article illustrate different stages of natural product-derived drug development. Each medicinal plant or fungus undergoes multiple stages of extraction, fractionation and purification of active compounds. At the same time these extracts, fractions and compounds are tested against different cancer models, from tumor-derived cell lines to animal models and clinical trials. Another dimension is studying the mechanisms-of-action and targets of the natural products and their derivatives. Maximum progress in all these trials brings us closer to a perfect natural drug for targeted cancer therapy. The mushroom discussed first in our review, Fomitopsis pinicola, is closer to the initial stages of involvement into modern cancer treatment: it is known to possess certain anticancer activities, and a set of compounds were isolated, but experiments on animal models and clinical trials are lacking, as well as precise studies on the molecular targets and signaling pathways affected by the fungus. Inonotus obliquus is a better-studied mushroom: here we have more data on mouse xenograft experiments and more molecular targets, including the Wnt/β-catenin pathway, a promising target for anticancer drugs of the future, but the medical relevance is still to be improved by clinical trials. Hericium erinaceus and especially Trametes versicolor are much more advanced in terms of medical applications due to their uncovered strong and complex immunomodulatory potential provided by rich polysaccharide and proteoglycan diversity. There are numerous clinical trials confirming applicability of these mushrooms and their extracts as components of modern anticancer chemotherapy. But the complex modes of action and molecular targets as well as exact structures of the active molecules from these mushrooms still have to be studied in more detail. In general, there has been a strong progress in the field of medicinal mushroom research in terms of anticancer drug development, but this work continues and much more progress still awaits us, especially in the fields of molecular targets of the medicinal mushrooms and the complex synergistic interplay of their different components.