Aqueous mistletoe extracts versus purified mistletoe lectin-I (pML-I): Effects on melanoma growth and spread in a human melanoma xenograft scid mouse model

Abstract

Objectives: Mistletoe extracts have been shown to provide eoxyribonucleic acid (DNA)-stabilizing effects in human periphral blood mononuclear cells (PBMC) in vitro. We investigated the ffect of amistletoe extract onPBMCwith andwithout concomitant reatment with cyclophosphamide and compared mitochondrial ctivity and replication of normal PBMC with that of a T-cell eukemia cell line. Design: The experiments were performed with PBMC of ealthy blood donors and the T-cell leukemia Jurkat cell ine. Cells were pre-incubated with mistletoe extract for 0–65h. 4-Hydroperoxycyclophosphamide (4-hpc, precursor of -hydroxycyclophosphamide)was added for 2h, after whichmitohondrial activity and replication were measured. All experiments ere randomized and blinded. Main outcomemeasures: Cell mitochondrial activity and repliation were assessed with spectrophotometric analysis of WsT-1 eduction and BrdU incorporation. Results: The application of 4-hpc consistently reduced mitohondrial activity and replication of PBMC and Jurkat cells. istletoe extract strongly enhanced PBMC mitochondrial activty and replication (with or without 4-hpc) and partially inhibited urkat cell replication (with 4-hpc only). Compared to mistleoe untreated cells, enhancement of PBMC mitochondrial activity y mistletoe extract was independent of treatment with 4-hpc, ut enhancement of PBMC replication by mistletoe extract was tronger when treated with 4-hpc. Conclusions: Mistletoe extract strongly stimulated healthy BMC but not malignant Jurkat cells. In addition, mistletoe extract eemed to partially protect healthy PBMC – but not malignant urkat cells – from the cytostatic effect of 4-hpc. The results motiate further preclinical and clinical investigations of mistletoe xtracts as an adjuvant medication in cancer therapy to alleviate ide effects of conventional therapy.