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


METHODS
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.


METHODS
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.
Burkhart
Jessica
J
Institute of Complementary Medicine KIKOM, University of Bern, Switzerland.
Wälchli
Chantal
C
Heusser
Peter
P
Weissenstein
Ulrike
U
Baumgartner
Stephan
S
Andres
Anne-Catherine
AC
D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology*; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D004359:Drug Therapy, Combination; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D014784:Mistletoe; D010936:Plant Extracts / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; C012358:4-hydroxycyclophosphamide; D003520:Cyclophosphamide