Chemoresistance is a challenge in cancer treatment, limiting the effectiveness of chemotherapy. Mushroom extracts have shown potential as treatments for cancer therapies, offering a possible solution to overcome chemoresistance. This systematic review aimed to explore the role of mushroom extracts in enhancing chemotherapy and reversing chemoresistance in cancer cells. We searched the PubMed, Web of Science and Scopus databases, following the PRISMA guidelines, and registered on PROSPERO. The extracts acted by inhibiting the proliferation of cancer cells, as well as enhancing the effect of chemotherapy. The mechanisms by which they acted included regulating anti-apoptotic proteins, inhibiting the JAK2/STAT3 pathway, inhibiting the ERK1/2 pathway, modulating microRNAs and regulating p-glycoprotein. These results highlight the potential of mushroom extracts to modulate multiple mechanisms in order to improve the efficacy of chemotherapy. This work sheds light on the use of mushroom extracts as an aid to chemotherapy to combat chemoresistance. Although studies are limited, the diversity of mushrooms and their bioactive compounds show promising results for innovative strategies to treat cancer more effectively. It is crucial to carry out further studies to better understand the therapeutic potential of mushroom extracts to improve the efficacy of chemotherapy in cancer cells.

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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.

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Despite considerable recent work to reveal different features of mushrooms species, the few studies of antiviral activities are inadequate and therefore further studies are required. Morchella conica, M. esculenta, Terfezia boudieri, Pleurotus ostreatus, Tricholoma anatolicum, Fomes fomentarius, Laetiporus sulphureus, Phellinus igniarius, Porodaedalea pini, and Pyrofomes demidoffii from Turkey were investigated to reveal their in vitro cytotoxic and anti-herpes simplex virus 1 (HSV-1) activities. The crude methanol extracts (MEs) and aqueous extracts (AEs) of fungal species and acyclovir (ACV) were used. Various dilutions were used to assess the cytotoxic effects of fungal species (50-0.10 mg/mL) and ACV (500-0.98 μg/mL) on uninfected Vero cells. Maximum nontoxic concentrations were determined for all extracts and ACV by comparing the optical densities of their cell controls. The concentration providing 50% protection against the cytopathic effect caused by the virus, extracts, and ACV (EC50) was calculated, and the half-maximal cytotoxic concentration (CC50) and the selectivity index (SI) were determined, the latter as the ratio of CC50 to EC50. While the AEs of F. fomentarius (EC50, 11.22 mg/mL; SI > 4.46), Ph. igniarius (EC50, 9.71 mg/mL; SI > 5.15), and P. pini (EC50, 7.16 mg/mL; SI > 6.98) showed considerable antiherpetic activity, MEs and AEs of the other fungal species did not showed any effects. The EC50 and SI of ACV were determined as 0.20 μg/mL and 3085, respectively. The results demonstrate that F. fomentarius, Ph. igniarius, and P. pini have important anti-HSV-1 activity.

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"Matsutake" mushrooms are formed by several species of Tricholoma sect. Caligata distributed across the northern hemisphere. A phylogenetic analysis of matsutake based on virtually neutral mutations in DNA sequences resolved robust relationships among Tricholoma anatolicum, Tricholoma bakamatsutake, Tricholoma magnivelare, Tricholoma matsutake, and Tricholoma sp. from Mexico (=Tricholoma sp. Mex). However, relationships among these matsutake and other species, such as Tricholoma caligatum and Tricholoma fulvocastaneum, were ambiguous. We, therefore, analyzed genomic copy numbers of σ marY1 , marY1, and marY2N retrotransposons by comparing them with the single-copy mobile DNA megB1 using real-time polymerase chain reaction (PCR) to clarify matsutake phylogeny. We also examined types of megB1-associated domains, composed of a number of poly (A) and poly (T) reminiscent of RNA-derived DNA elements among these species. Both datasets resolved two distinct groups, one composed of T. bakamatsutake, T. fulvocastaneum, and T. caligatum that could have diverged earlier and the other comprising T. magnivelare, Tricholoma sp. Mex, T. anatolicum, and T. matsutake that could have evolved later. In the first group, T. caligatum was the closest to the second group, followed by T. fulvocastaneum and T. bakamatsutake. Within the second group, T. magnivelare was clearly differentiated from the other species. The data suggest that matsutake underwent substantial evolution between the first group, mostly composed of Fagaceae symbionts, and the second group, comprised only of Pinaceae symbionts, but diverged little within each groups. Mobile DNA markers could be useful in resolving difficult phylogenies due to, for example, closely spaced speciation events.

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Tricholoma matsutake produces commercially valuable, yet uncultivable, mushrooms (matsutake) in association with pines in the Far East and Scandinavia and with both pines and oaks in the foothills of Tibet. Other matsutake mushrooms, such as Tricholoma anatolicum from the Mediterranean regions and Tricholoma magnivelare and Tricholoma sp. from the North Pacific Coast area of Canada and North America as well as Mexico, respectively, are associated with pines or oaks in their natural habitats. Tricholoma bakamatsutake and Tricholoma fulvocastaneum from Asia produce moderately valuable matsutake mushrooms and are solely associated with Fagaceae in nature. In this study, we demonstrate for the first time that matsutake mushrooms from Scandinavia, Mediterranean regions, North America, and Tibet form ectomycorrhizae with Pinus densiflora similar to the Far East T. matsutake. In general, worldwide T. matsutake and the symbionts of Pinaceae colonize the rhizospheres of P. densiflora as well as T. matsutake isolated from the host plant. However, T. fulvocastaneum and T. bakamatsutake formed a discontinuous Hartig net and no Hartig net, respectively, and colonized to a lesser extent as compared to T. matsutake. The data suggest that conifer-associated matsutake mushrooms in their native habitat will associate symbiotically with the Asian red pine.

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