Anticancer potentiality and mode of action of low-carbohydrate proteins and peptides from mushrooms

Severe side effects of chemotherapy as well as drug resistance highlight the ongoing need to discover novel natural bioactive compounds with anticancer potentiality. Mushroom-derived proteins are among the naturally occurring compounds that have been the subject of a body of research on their potentiality in cancer therapy. The greatest attention in relevant review articles has been paid to well-known mushroom-derived glycoproteins such as lectins and protein-bound polysaccharide complexes such as polysaccharide-K (PSK) or krestin and polysaccharopeptide (PSP), which contain substantial amounts of carbohydrates (50-90%). These complex compounds exert their anticancer activity mainly by binding to cell membranes leading to extrinsic (death receptor) apoptosis or intrinsic (mitochondrial) apoptotic pathways. However, several other research studies have reported pure, well-characterized, proteins or peptides from mushrooms, which are carbohydrate-free or have very low amounts of carbohydrate. These proteins may fall into four categories including fungal immunomodulatory proteins, ubiquitin-like proteins, enzymes, and unclassified proteins. Well-defined chemical structure, elucidated full amino acid or N-terminal sequences, purity, and having some distinct and specific pathways compared to glycoproteins have made these low-carbohydrate proteins attractive for cancer research. The aim of this review was therefore to improve the current understanding of mushroom-derived low-carbohydrate proteins and to consolidate the existing knowledge of the most promising mushroom species from which low-carbohydrate proteins have been derived, characterized, and examined for their anticancer activity. In addition, molecular targets and mechanisms of action of these proteins have been discussed. Key points • Mushroom-derived low-carbohydrate proteins lack or have low carbohydrate. • Low-carbohydrate proteins show potent anticancer activities in vitro and in vivo. • There are specific pathways for low-carbohydrate proteins to inhibit cancer cells.