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Experimental Therapeutics
Recombinant mistletoe lectin induces p53-independent apoptosis in tumour cells and cooperates with ionising radiation
K Hostanska1, V Vuong2, S Rocha2,4, M S Soengas3, C Glanzmann2, R Saller1, S Bodis2 and M Pruschy2
1Department of Internal Medicine, University Hospital Zurich, Raemistr. 100, CH-8091 Zurich, Switzerland
2Department of Radiation Oncology, University Hospital Zurich, Raemistr. 100, CH-8091 Zurich, Switzerland
3Department of Dermatology, University of Michigan Health System, Ann Arbor, MI 48109, USA
Correspondence to: Dr M Pruschy, E-mail: martin.pruschy@dmr.usz.ch
4Current address: Department of Biochemistry, University of Dundee, Dundee DD1 5EH, UK.
Abstract
Mistletoe extracts are used as alternative cancer treatment in addition to standard chemotherapy and radiation treatment and have an immunostimulatory and pain-relieving effect.
A direct antitumour effect of mistletoe extracts against tumour cells of lymphoid origin has been linked to the D-galactoside-specific mistletoe lectin I. In this study, we investigated the cellular effect of bacterially expressed, recombinant mistletoe lectin alone or in combination with ionising radiation in a genetically defined p53-wild-type and p53-deficient E1A/ras-transformed murine tumour cells system.
Downregulation of the proliferative activity and cell killing by recombinant mistletoe lectin occurred in a clear dose response (0.1-1 ng ml-1). Induction of apoptosis was p53-independent, but apoptosis-associated factor-1-dependent.
Cellular treatment with lectin in combination with ionising radiation resulted in both p53-wild-type and p53-deficient tumour cells in an at least additive, antiproliferative effect and enhanced activation of caspase-3.
Combined treatment with ionising radiation and lectin revealed a similar cytotoxic effect in human, p53-mutated adenocarcinoma cells. Thus, recombinant mistletoe lectin alone and in combination with ionising radiation bypasses often prevalent apoptotic deficiencies in treatment-resistant tumour cells.
British Journal of Cancer (2003) 88, 1785-1792.
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