Differential effects of Viscum album extract IscadorQu on cell cycle progression and apoptosis in cancer cells.
Extracts from European mistletoe or Viscum album L. have been reported to exert cytotoxic and immunomodulatory effects in vitro and in vivo. The mechanism of this anti-tumoral activity is however, largely unknown. In this study we tested the hypothesis that IscadorQu, an aqueous fermented extract from the European mistletoe grown on oaks, induces tumor regression by cell cycle inhibition and/or interference with apoptotic signaling pathways in cancer cells. Also a possible effect on angiogenesis, which is a prerequisite for tumor growth in vivo, is studied in endothelial cell cultures. Furthermore, we examined which apoptotic signaling route is activated by staining cells for specific pro-apoptotic proteins. To characterize these properties, 6 different human cancer cell lines, one epidermis derived cell line and 2 endothelial cell cultures were incubated with different concentrations of IscadorQu. Cell cycle kinetics parameters were measured by bromodeoxyuridine (BrdU) pulse labeling and tubulin staining. Apoptotic responses were detected by M30 CytoDeath or Annexin V/propidium iodide assays. Characterization of the apoptotic pathway was performed by staining cells for active caspase 3, active caspase 8, cytochrome C and chloromethyl-X-rosamine. The results of this study show that sensitivity to IscadorQu treatment varies strongly between different cell lines. In sensitive cell lines, including tumor and endothelial cell cultures, IscadorQu caused early cell cycle inhibition followed by apoptosis in a dose-dependent manner. Apoptosis was induced by activating the mitochondrial but not the death receptor-dependent pathway.
Harmsma
Marjan
M
Department of Molecular Cell Biology, Research Institute for Growth and Development (GROW), University of Maastricht, The Netherlands. marjan.harmsma@molcelb.unimaas.nl
Grommé
Monique
M
Ummelen
Monique
M
Dignef
Wendy
W
Tusenius
Karel Jan
KJ
Ramaekers
Frans C S
FC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*; D010940:Plant Proteins / Q000494:pharmacology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010936:Plant Extracts; D010940:Plant Proteins; C077177:viscum album peptide