Rongchen Dai,1,† Mengfan Liu,1,† Wan Najbah Nik Nabil,1,2 Zhichao Xi,1,* and Hongxi Xu3,*
Abstract
Mycomedicine is a unique class of natural medicine that has been widely used in Asian countries for thousands of years. Modern mycomedicine consists of fruiting bodies, spores, or other tissues of medicinal fungi, as well as bioactive components extracted from them, including polysaccharides and, triterpenoids, etc. Since the discovery of the famous fungal extract, penicillin, by Alexander Fleming in the late 19th century, researchers have realised the significant antibiotic and other medicinal values of fungal extracts. As medicinal fungi and fungal metabolites can induce apoptosis or autophagy, enhance the immune response, and reduce metastatic potential, several types of mushrooms, such as Ganoderma lucidum and Grifola frondosa, have been extensively investigated, and anti-cancer drugs have been developed from their extracts. Although some studies have highlighted the anti-cancer properties of a single, specific mushroom, only limited reviews have summarised diverse medicinal fungi as mycomedicine. In this review, we not only list the structures and functions of pharmaceutically active components isolated from mycomedicine, but also summarise the mechanisms underlying the potent bioactivities of several representative mushrooms in the Kingdom Fungi against various types of tumour.
1. Introduction
Currently, cancers contribute to the second leading cause of death worldwide and involve a series of complex pathogenic mechanisms [1]. Despite the considerable advancements in anti-cancer therapy, serious problems persist. Chemotherapy and radiation therapy, as examples, remain the main strategies for cancer management. Nevertheless, the effectiveness of synthetic anti-cancer agents for chemotherapy is often limited owing to their serious toxic effects, affecting the metabolism and proliferation of normal tissues, and reducing the quality of life of patients. Therefore, alternative therapeutic approaches for cancer treatment are urgently required.
Since ancient times, the medicinal values of natural products have been acknowledged. A wide range of natural products, including plant- and marine-organism-derived agents, are gaining momentum in anti-cancer therapy owing to their unique advantages of high efficiency and minimal side effects [2]. Mycomedicine, a unique class of natural medicines that includes numerous edible mushrooms and medicinal fungi, as well as their metabolites, has been widely employed for treating different kinds of diseases for thousands of years according to Shen Nong’s Materia Medica [3]. In China, six medicinal fungi have been included in the China Pharmacopoeia, including Ganoderma lucidum, which has been extensively researched and has many clinical applications, especially as an anti-cancer agent (Figure 1). Modern technologies have identified that pharmaceutically active compounds isolated from mycomedicine predominantly include triterpenoids, polysaccharides, and proteins. The active ingredients and anti-cancer properties of some of the medicinal fungi have been well elaborated in recent review articles [4,5,6,7,8]. However, a detailed review of numerous anti-tumour bioactivities of various mycomedicines is lacking. In the current review, we discuss nearly 20 kinds of typical mycomedicines worldwide that have exhibited promising bioactivities against tumors (Table 1). More importantly, we provide a detailed summary of the mycomedicine-derived bioactive components, as well as their underlying anti-cancer mechanisms, such as those involved in regulating cancer cell cycle arrest, apoptosis, autophagy, the immune response, metastasis, angiogenesis, oxidation, the gut microenvironment, and multidrug resistance of multiple famous mycomedicines (Table 2, Figure 2). Furthermore, we discuss the current clinical evidence of mycomedicine in anti-cancer therapy.
An overview of the numerous anti-tumour bioactivities of Ganoderma lucidum. Pharmaceutically active components isolated from Ganoderma lucidum demonstrated potent anti-tumour bioactivities through multiple signalling pathways. “↑” represents activate, promote, stimulate or up-regulate, while “Т” represents inhibit, suppress, decrease or down-regulate.
The schematic diagram of the anti-tumour bioactivities of mycomedicine. Mycomedicine demonstrated anti-cancer activities through regulation of cell cycle, apoptosis, autophagy, angiogenesis, oxidative stress, metastasis, multidrug resistance and gut microenvironment. “↑” indicates activate, promote, stimulate or up-regulate, while “↓” and “T” indicates inhibit, suppress, decrease or down-regulate.