title: Small, novel proteins from the mistletoe Phoradendron tomentosum exhibit highly selective cytotoxicity to human breast cancer cells.
abstract: Four novel proteins (phoratoxins C-F) have been isolated from the North American mistletoe Phoradendron tomentosum. The amino acid sequences of these phoratoxins were determined unambiguously using a combination of Edman degradation and trypsin enzymatic digestion, and by electrospray ionization tandem mass spectrometry sequencing. Phoratoxins C, E and F consist of 46 amino acid residues; and phoratoxin D of 41. All proteins had six cysteines, similar to the earlier described phoratoxins A and B, which are thionins. The cytotoxicity of each protein was evaluated in a human cell line panel that represented several cytotoxic drug-resistance mechanisms. For the half-maximal inhibitory concentrations (IC50 values) of the different cell lines in the panel, correlation with those of standard drugs was low. The most potent cytotoxic phoratoxin C was further tested on primary cultures of human tumor cells from patients. The solid tumor samples from breast cancer cells were 18 times more sensitive to phoratoxin C than the tested hematological tumor samples.
authors.affiliation: Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, PO Box 574, 751 23 Uppsala, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Johansson
authors.forename: J
authors.initials: J
authors.lastname: Gullbo
authors.forename: P
authors.initials: P
authors.lastname: Lindholm
authors.forename: B
authors.initials: B
authors.lastname: Ek
authors.forename: E
authors.initials: E
authors.lastname: Thunberg
authors.forename: G
authors.initials: G
authors.lastname: Samuelsson
authors.forename: R
authors.initials: R
authors.lastname: Larsson
authors.forename: L
authors.initials: L
authors.lastname: Bohlin
authors.forename: P
authors.initials: P
authors.lastname: Claeson
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy; D003545:Cysteine / Q000737:chemistry; D006801:Humans; D014784:Mistletoe / Q000737:chemistry*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010936:Plant Extracts / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D010940:Plant Proteins; C008873:phoratoxin protein, Phoradendron tomentosum; D003545:Cysteine