Mushroom-Derived Compounds as Metabolic Modulators in Cancer

Cancer is responsible for lifelong disability and decreased quality of life. Cancer-associated changes in metabolism, in particular carbohydrate, lipid, and protein, offer a new paradigm of metabolic hits. Hence, targeting the latter, as well as related cross-linked signalling pathways, can reverse the malignant phenotype of transformed cells. The systemic toxicity and pharmacokinetic limitations of existing drugs prompt the discovery of multi-targeted and safe compounds from natural products. Mushrooms possess biological activities relevant to disease-fighting and to the prevention of cancer. They have a long-standing tradition of use in ethnomedicine and have been included as an adjunct therapy during and after oncological care. Mushroom-derived compounds have also been reported to target the key signature of cancer cells in in vitro and in vivo studies. The identification of metabolic pathways whose inhibition selectively affects cancer cells appears as an interesting approach to halting cell proliferation. For instance, panepoxydone exerted protective mechanisms against breast cancer initiation and progression by suppressing lactate dehydrogenase A expression levels and reinducing lactate dehydrogenase B expression levels. This further led to the accumulation of pyruvate, the activation of the electron transport chain, and increased levels of reactive oxygen species, which eventually triggered mitochondrial apoptosis in the breast cancer cells. Furthermore, the inhibition of hexokinase 2 by neoalbaconol induced selective cytotoxicity against nasopharyngeal carcinoma cell lines, and these effects were also observed in mouse models. Finally, GL22 inhibited hepatic tumour growth by downregulating the mRNA levels of fatty acid-binding proteins and blocking fatty acid transport and impairing cardiolipin biosynthesis. The present review, therefore, will highlight how the metabolites isolated from mushrooms can target potential biomarkers in metabolic reprogramming