Small, novel proteins from the mistletoe Phoradendron tomentosum exhibit highly selective cytotoxicity to human breast cancer cells.
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.
Johansson
S
S
Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, PO Box 574, 751 23 Uppsala, Sweden.
Gullbo
J
J
Lindholm
P
P
Ek
B
B
Thunberg
E
E
Samuelsson
G
G
Larsson
R
R
Bohlin
L
L
Claeson
P
P
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
D000970:Antineoplastic Agents; D010936:Plant Extracts; D010940:Plant Proteins; C008873:phoratoxin protein, Phoradendron tomentosum; D003545:Cysteine