Mistletoe lectin-I augments antiproliferative effects of the PPARgamma agonist rosiglitazone on human malignant melanoma cells.
As malignant melanoma cells are highly resistant to conventional chemotherapy, survival rates after tumor spread remain poor and hence there is an urgent need for new therapeutic options. For both mistletoe lectin-I (ML-I) and the thiazolidinediones as synthetic ligands of the peroxisome proliferator-activated receptor gamma (PPARgamma) an antiproliferative effect on malignant melanoma cells has previously been shown. Hence, the aim of this study was to investigate whether the combination of ML-I and the PPARgamma ligand rosiglitazone is more efficacious in the treatment of malignant melanoma cells than either agent alone. Proliferation of three human melanoma cell lines treated with ML-I, rosiglitazone and the combination of both was measured in a broad concentration range (0.0001-100 microg/mL) using the XTT cell proliferation assay. Combined application tremendously increased the antiproliferative effect on all three melanoma cell lines compared with single agent treatment. In comparison with the single use of rosiglitazone, the combination with ML-I significantly increased the inhibition of cell growth by 51-79% and in comparison with the single use of ML-I by 9-32%, respectively. In conclusion, this study shows that the combination of ML-I with rosiglitazone significantly augments their antiproliferative effect on malignant melanoma cells in comparison with their single agent application, which might be a promising tool for further therapeutic studies.
Freudlsperger
Christian
C
Institute of Anatomy II, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. christian.freudlsperger@klinikum.uni-tuebingen.de
Dahl
Anka
A
Hoffmann
Juergen
J
Reinert
Siegmar
S
Schumacher
Udo
U
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D054790:Ribosome Inactivating Proteins, Type 2 / Q000494:pharmacology / Q000627:therapeutic use*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D014118:Toxins, Biological / Q000494:pharmacology / Q000627:therapeutic use*; D028182:Viscum album / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D047495:PPAR gamma; D010936:Plant Extracts; D054790:Ribosome Inactivating Proteins, Type 2; D045162:Thiazolidinediones; D014118:Toxins, Biological; C488862:mistletoe lectin I; D000077154:Rosiglitazone