1. ¹Department of Internal Medicine, University Hospital Zurich, Raemistr. 100, CH-8091 Zurich, Switzerland
2. ²Department of Radiation Oncology, University Hospital Zurich, Raemistr. 100, CH-8091 Zurich, Switzerland
3. ³Department of Dermatology, University of Michigan Health System, Ann Arbor, MI 48109, USA

Correspondence: Dr M Pruschy, E-mail: martin.pruschy@dmr.usz.ch

⁴Current address: Department of Biochemistry, University of Dundee, Dundee DD1 5EH, UK.

Received 1 November 2002; Revised 10 March 2003; Accepted 18 March 2003.

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.