doi: 10.18632/oncotarget.25660

Published online 2018 Jun 26

Artem Blagodatski,^1,2,* Margarita Yatsunskaya,^3,* Valeriia Mikhailova,¹ Vladlena Tiasto,¹ Alexander Kagansky,¹ and Vladimir L. Katanaev¹

Abstract

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.

Keywords: cancer, fungotherapy, medicinal mushrooms, targeted treatment, biomedicine

INTRODUCTION

Nature has since long been an important source of inspiration for the medicine. Throughout evolution, nature produces a vast diversity of biologically active substances, which possess enormous therapeutic potential, amongst other things regarding the treatment of cancers. Natural products have already yielded a series of compounds widely used in anticancer chemotherapy, whilst application of such products in folk and traditional medicine has always been an important clue pointing to potential new sources of compounds with therapeutic potential. Well-known examples include camptothecin derived from the bark and stem of the tree Camptotheca acuminata used in Chinese traditional medicine [1], vinca alcaloids derived from Madagascan periwinkle [2] or taxanes derived from the Pacific Yew [3]. Nevertheless, such “first-generation” natural chemotherapeutic agents are directed mostly against housekeeping processes (such as DNA replication or microtubule polymerization and stabilization), which are more active against fast proliferating cancer cells, but are in no way cancer-specific. This results in a variety of harmful side effects in the conventional anticancer chemotherapy, up to eventual patient’s death due to overdose. More up-to-date approaches to cancer treatment involve targeted therapies specific to the hallmarks of cancer and harmless or of low harm to the healthy tissues [4]. Search for compounds able to selectively act on cancer cells or on tumorigenic processes is therefore a problem of the highest priority in the field. Thus, it is a task of great importance to “mine the treasury” of natural products for such compounds in order to expand the arsenal of modern oncology with a variety of highly specific tools.

Cancer fungotherapy is a promising scientific field, which deals with antitumor substances derived from mushrooms. It has been an integral part of the world traditional medicine since the antiquity [5].

The concept of fungal treatment officially appeared in Traditional Chinese Medicine and can be dated back to several thousand years ago [6]. The ancient Chinese pharmacopoeia included hundreds of herbal and fungal species – the latter were considered to be the most effective natural remedies for various types of tumors [6]. In other countries of East and Southeast Asia, mushrooms were also highly valued and rated as “beneficial to health” for centuries. Plant and fungal products were also widespread in Russia, representing the main medicinal resources until the 18^th century [7].

In the middle of the 20^th century, some of the earliest scientific research was performed on Boletus edulis in order to study the antitumor activity of edible and medicinal mushrooms [8].

Over the past 60 years, the rate of studies focusing on fungi increased exponentially, but in many areas of research mushrooms as potential source for beneficial products are still ignored. For instance, 90% of fungal species were never analyzed with respect to their antibiotic and antitumor activity. Moreover, a large part of cancer-related investigations done on fungi deals merely with characterization of unspecific cytotoxic or cytostatic effects on cancer cells (such effects would be harmful for healthy cells as well), rather than with modulation of specific oncogenic signaling pathways, which could be targets for modern, highly specific anticancer therapies. Importantly, a tumor has many “weak spots” and can be targeted at different levels, such as tumor-specific pro-proliferation signaling, regulation of apoptosis, cancer-specific metabolism, angiogenesis, metastasis and, last but not least, modulation of the immune system. The peculiarity of medicinal mushrooms is that, being producers of hundreds of compounds, they can affect multiple cancer-related processes in synergistic ways when used as a treatment. Thus, not only studies of certain fungal-derived compounds are important, but also research on complex anticancer effects caused by the combinations of molecules in their extracts is of a high interest.

In this review, we intend to analyze the recent knowledge, potential to cover the abovementioned processes on the example of four Basidiomycota mushrooms: Fomitopsis pinicola, Hericium erinaceus, Trametes versicolor and Inonotus obliquus. The fields of cancer fungotherapy and of search for novel antitumor agents are by far not limited to these species; however, these four can serve as typical representatives of widespread medicinal mushrooms used both in traditional medicine and in modern biomedical research. They belong to three different orders, and are a rich source of bioactive compounds such as polyphenols, polysaccharides, glucans, terpenoids, steroids, cerebrosides and proteins, which can be used for treatment of various cancers (Table ​(Table1).1). We chose these representatives to convexly illustrate the therapeutic potential of the fungi and fungal-derived products in relation to cancer and to inspire further interdisciplinary work at the junction of oncology and mycology, which should result in future discoveries of novel low-toxic drugs with highly specific antitumor activities.

Reference:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044372/