Mistletoe lectins: From interconnecting proteins to potential tumour inhibiting agents

Background: Mistletoe lectins (MLs) are obtained from the diverse species of Viscum album L., sharing an extensive history of their use as potent anticancer agents in the prevention and treatment of various cancers. Mistletoe lectin-I (ML-I) is highly investigated among all MLs for the anti-proliferative activity that arises from its cytotoxic and immunomodulatory functions. Methods: Various databases, such as PubMed, Scopus, Web of Science, and Google Scholar, were searched up to 2020 using relevant keywords. Results: In vitro and in vivo studies have signified apoptosis and cytokine production by immune cells as main mechanisms responsible for antitumor activities. MLs elicit the apoptotic pathway in tumour cell by regulating the expression of genes resulting in activation of caspases causing cell death. During apoptosis the disruption of the mitochondrial membrane leads to the release of cytochrome C and pro apoptotic factor Apaf-1 causing activation of Caspases. In addition, studies conducted on animal models have suggested that c-Myc, JNK and immune signalling systems as main oncotargets that mediate the antitumor functions. MLs are known to regulate the expression of genes involved in tumour survival, spread and growth. This includes down-regulation of anti-apoptotic proteins (Bcl-2), metalloproteinases, c-Myc protein, growth factor β genes while as up-regulation of pro-apoptotic proteins (Bax, Bad) and tumour necrosis factor (TNF).Transcriptomic and proteomic data also reported that cancer cells treated with whole plant Mistletoe extract constituting liphophillic Mistletoe compounds (triterpenes) and water soluble (lectins and viscotoxins) showed better anticancer efficacy than individual components while significantly affecting the genes involved in cell survival and death. Conclusion: This review aims at exploring the antitumor mechanisms of MLs against various cancer cell lines and mice animal models which encourages its application as effective bio-therapeutic tools to address range of human cancers