Industrial Fungi Biotechnology Research Department, Research Institute for Industrial Biotechnology, Academic Center for Education, Culture and Research (ACECR), Khorasan Razavi Branch, P.O. Box 91775-1376, Mashhad, Iran.
Integrative Oncology Department, Breast Cancer Research Center, Moatamed Cancer Institute, ACECR, Tehran, Iran.
Appl Microbiol Biotechnol. 2020 Aug;104(16):6855-6871. doi: 10.1007/s00253-020-10707-8. Epub 2020 Jun 15.
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.
化疗的严重副作用和耐药性突显了持续发现具有抗癌潜力的新型天然生物活性化合物的必要性。从蘑菇中提取的蛋白质是天然存在的化合物之一，已经成为癌症治疗潜力研究的主题。在相关的综述文章中，最受关注的是众所周知的蘑菇衍生糖蛋白，如凝集素和蛋白结合多糖复合物，如多糖-K（PSK）或克雷斯汀和多糖肽（PSP），它们含有大量的碳水化合物（50-90%）。这些复杂的化合物主要通过与细胞膜结合发挥其抗癌活性，导致外在（死亡受体）凋亡或内在（线粒体）凋亡途径。然而，其他一些研究报告了来自蘑菇的纯、特征明确的蛋白质或肽，它们不含碳水化合物或碳水化合物含量非常低。这些蛋白质可能分为四类，包括真菌免疫调节蛋白、泛素样蛋白、酶和未分类的蛋白质。与糖蛋白相比，明确的化学结构、阐明的完整氨基酸或 N 端序列、纯度以及具有一些独特和特定的途径，使这些低碳水化合物蛋白质成为癌症研究的热门选择。因此，本综述的目的是提高对蘑菇衍生的低碳水化合物蛋白质的现有认识，并整合从最有前途的蘑菇物种中提取、表征和研究其抗癌活性的低碳水化合物蛋白质的现有知识。此外，还讨论了这些蛋白质的分子靶点和作用机制。要点：
蘑菇衍生的低碳水化合物蛋白质缺乏或含有低聚糖。
低碳水化合物蛋白质在体外和体内均表现出很强的抗癌活性。
低碳水化合物蛋白质有抑制癌细胞的特定途径。
