In vitro investigation into the potential of a mistletoe extract to alleviate adverse effects of cyclophosphamide

Altern Ther Health Med. 2010 May-Jun;16(3):40-8.


Objectives: Mistletoe extracts have been shown to provide deoxyribonucleic acid (DNA)-stabilizing effects in human peripheral blood mononuclear cells (PBMC) in vitro. We investigated the effect of a mistletoe extract on PBMC with and without concomitant treatment with cyclophosphamide and compared mitochondrial activity and replication of normal PBMC with that of a T-cell leukemia cell line.

Design: The experiments were performed with PBMC of healthy blood donors and the T-cell leukemia Jurkat cell line. Cells were pre-incubated with mistletoe extract for 60 to 65 hours. 4-hydroperoxycyclophosphamide (4-hpc, precursor of 4-hydroxycyclophosphamide) was added for 2 hours, after which mitochondrial activity and replication were measured. All experiments were randomized and blinded.

Main outcome measures: Cell mitochondrial activity and replication were assessed with spectrophotometric analysis of WST-1 reduction and BrdU incorporation.

Results: The application of 4-hpc consistently reduced mitochondrial activity and replication of PBMC and Jurkat cells. Mistletoe extract strongly enhanced PBMC mitochondrial activity and replication (with or without 4-hpc) and partially inhibited Jurkat cell replication (with 4-hpc only). Compared to mistletoe untreated cells, enhancement ofPBMC mitochondrial activity by mistletoe extract was independent of treatment with 4-hpc, but enhancement of PBMC replication by mistletoe extract was stronger when treated with 4-hpc.

Conclusions: Mistletoe extract strongly stimulated healthy PBMC but not malignant Jurkat cells. In addition, mistletoe extract seemed to partially protect healthy PBMC-but not malignant Jurkat cells-from the cytostatic effect of 4-hpc. The results motivate further preclinical and clinical investigations of mistletoe extracts as an adjuvant medication in cancer therapy to alleviate side effects of conventional therapy.

MeSH terms

  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cells, Cultured
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / analogs & derivatives*
  • Cyclophosphamide / pharmacology
  • Drug Therapy, Combination
  • Humans
  • Jurkat Cells / drug effects
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy*
  • Leukocytes, Mononuclear / drug effects
  • Lymphocyte Activation / drug effects
  • Mistletoe*
  • Plant Extracts / pharmacology*


  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • 4-hydroxycyclophosphamide
  • Cyclophosphamide