Mistletoe lectin II (ML II)

Mistletoe lectin II (ML II) is a major bioactive glycoprotein derived from the European mistletoe (Viscum album) and is a member of the type II ribosome-inactivating protein (RIP) family [1, 7]. It possesses a heterodimeric structure consisting of a toxic A-chain with N-glycosylase activity and a carbohydrate-binding B-chain [1, 9]. The B-chain specifically recognizes and binds to cell-surface D-galactose and N-acetyl-D-galactosamine residues, facilitating the protein's entry into the cell through receptor-mediated endocytosis [1, 3]. Once in the cytosol, the A-chain inhibits protein synthesis by depurinating the 28S ribosomal RNA, which triggers cellular stress and leads to apoptosis in cancer cells [7, 12]. In addition to its direct cytotoxicity, ML II acts as a potent immunomodulator by stimulating natural killer (NK) cells, T-lymphocytes, and the production of pro-inflammatory cytokines like IL-6 and TNF-alpha [1, 4, 8]. Clinical applications of ML II, typically as part of standardized mistletoe extracts such as Iscador or Helixor, focus on its role as an adjuvant therapy in oncology to improve quality of life and support the immune response [11, 13, 16]. Potential safety concerns include local injection site reactions, fever, and rare but serious hypersensitivity reactions, as well as transient hepatotoxicity observed at high intravenous doses [10, 14].

Other names

Viscum album lectin IIML-IIVAL-IIViscumin IIMistletoe lectin 2

Mistletoe lectin II acts as a type II ribosome-inactivating protein (RIP) [1, 7]. The B-chain binds to cell-surface D-galactose and N-acetyl-D-galactosamine residues, promoting internalization via receptor-mediated endocytosis [1, 3]. After translocation to the cytosol, the A-chain functions as an N-glycosylase that depurinates the sarcin/ricin loop of 28S ribosomal RNA, irreversibly inhibiting protein synthesis and inducing apoptosis [4, 7, 13]. It also exerts immunomodulatory effects by acting as a pattern recognition receptor ligand and stimulating NK cells and cytokine release [1, 4].