Cellular and Molecular Life Sciences CMLS

, Volume 60, Issue 1, pp 165–175

Small, novel proteins from the mistletoe Phoradendron tomentosum exhibit highly selective cytotoxicity to human breast cancer cells

  • S. Johansson
  • J. Gullbo
  • P. Lindholm
  • B. Ek
  • E. Thunberg
  • G. Samuelsson
  • R. Larsson
  • L. Bohlin
  • P. Claeson
Research Article

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.

Key words. Breast cancer; cytotoxicity drug screening; mistletoe proteins; Phoradendron tomentosum; phoratoxins; thionins; tumor cell lines. 

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Copyright information

© Birkhäuser Verlag, 2003

Authors and Affiliations

  • S. Johansson
    • 1
  • J. Gullbo
    • 2
  • P. Lindholm
    • 1
  • B. Ek
    • 3
  • E. Thunberg
    • 1
  • G. Samuelsson
    • 1
  • R. Larsson
    • 2
  • L. Bohlin
    • 1
  • P. Claeson
    • 1
  1. 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.seSE
  2. 2.Division of Clinical Pharmacology, University Hospital, Uppsala University, Uppsala (Sweden)SE
  3. 3.Uppsala Genetic Center, Department of Plant Biology, Swedish University of Agricultural Science, Uppsala (Sweden)SE

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