Mistletoe lectin III (ML-III)

Mistletoe lectin III (ML-III) is a type II ribosome-inactivating protein (RIP) derived from the European mistletoe plant, Viscum album. It is a heterodimeric glycoprotein consisting of a toxic A-chain with enzymatic activity and a B-chain that acts as a carbohydrate-binding lectin specifically recognizing N-acetylgalactosamine and D-galactose residues [4, 10]. The B-chain enables the molecule to bind to the surface of host cells and undergo endocytosis, allowing the A-chain to reach the cytosol where it halts protein synthesis by damaging the 28S rRNA [7, 10]. This mechanism induces potent cytotoxic effects, making it a key active component in mistletoe-based adjuvant cancer therapies. In a clinical context, ML-III is used primarily as an immunomodulatory and cytotoxic agent within standardized mistletoe extracts to support conventional cancer treatments such as chemotherapy and radiation [1, 12]. It is known to enhance the immune response by promoting the maturation of dendritic cells and the activation of natural killer cells and T-lymphocytes [2, 14]. While generally well-tolerated at therapeutic doses, it can cause side effects ranging from local inflammatory reactions at the site of injection to systemic symptoms like fever or hypersensitivity [11, 12]. Recent research has also highlighted its potential in inducing immunogenic cell death, further positioning it as a tool for integrative oncology [2, 14].

Other names

Viscum album lectin 3ML-3N-acetylgalactosamine-specific mistletoe lectinViscumin (total extract component)

The B-chain of Mistletoe lectin III binds to cell-surface glycoproteins and glycolipids with terminal N-acetylgalactosamine or D-galactose residues, facilitating entry via receptor-mediated endocytosis [4, 10]. Once in the cytosol, the A-chain exerts RNA N-glycosidase activity, depurinating the A4324 residue of the 28S ribosomal RNA sarcin/ricin loop, which irreversibly inhibits protein synthesis [4, 7, 10]. This cellular stress triggers the intrinsic and extrinsic apoptotic pathways, leading to programmed cell death in target tumor cells [5, 6]. Additionally, it acts as an immunomodulator by stimulating the release of cytokines (IL-1, IL-6, TNF-alpha) and enhancing the activity of natural killer (NK) cells and T-lymphocytes [4, 14].