Small,novel proteins from the mistletoe <Emphasis Type="Italic">Phoradendron tomentosum</Emphasis> exhibit highly selective cytotoxicity to human breast cancer cells |
| |
Authors: | S Johansson J Gullbo P Lindholm B Ek E Thunberg G Samuelsson R Larsson L Bohlin P Claeson |
| |
Institution: | (1) Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, PO Box 574, 751 23 Uppsala (Sweden), Fax: + 46 18 509101, e-mail: per.claeson@mpa.se, SE;(2) Division of Clinical Pharmacology, University Hospital, Uppsala University, Uppsala (Sweden), SE;(3) Uppsala Genetic Center, Department of Plant Biology, Swedish University of Agricultural Science, Uppsala (Sweden), SE |
| |
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.
Received 30 September 2002; received after revision 28 October 2002; accepted 7 November 2002
RID="*"
ID="*"Corresponding author. |
| |
Keywords: | , Breast cancer, cytotoxicity drug screening, mistletoe proteins, Phoradendron tomentosum, phoratoxins, thionins,,,,,,tumor cell lines, |
本文献已被 PubMed SpringerLink 等数据库收录! |
|