Differential effects of Viscum album extract Iscador®Qu on cell cycle progression and apoptosis in cancer cells

  • Authors:
    • Marjan Harmsma
    • Monique Grommé
    • Monique Ummelen
    • Wendy Dignef
    • Karel Jan Tusenius
    • Frans C.S. Ramaekers
  • View Affiliations

  • Published online on: December 1, 2004     https://doi.org/10.3892/ijo.25.6.1521
  • Pages: 1521-1529
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Abstract

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 Iscador®Qu, 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.

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December 2004
Volume 25 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Harmsma M, Grommé M, Ummelen M, Dignef W, Tusenius KJ and Ramaekers FC: Differential effects of Viscum album extract Iscador®Qu on cell cycle progression and apoptosis in cancer cells. Int J Oncol 25: 1521-1529, 2004
APA
Harmsma, M., Grommé, M., Ummelen, M., Dignef, W., Tusenius, K.J., & Ramaekers, F.C. (2004). Differential effects of Viscum album extract Iscador®Qu on cell cycle progression and apoptosis in cancer cells. International Journal of Oncology, 25, 1521-1529. https://doi.org/10.3892/ijo.25.6.1521
MLA
Harmsma, M., Grommé, M., Ummelen, M., Dignef, W., Tusenius, K. J., Ramaekers, F. C."Differential effects of Viscum album extract Iscador®Qu on cell cycle progression and apoptosis in cancer cells". International Journal of Oncology 25.6 (2004): 1521-1529.
Chicago
Harmsma, M., Grommé, M., Ummelen, M., Dignef, W., Tusenius, K. J., Ramaekers, F. C."Differential effects of Viscum album extract Iscador®Qu on cell cycle progression and apoptosis in cancer cells". International Journal of Oncology 25, no. 6 (2004): 1521-1529. https://doi.org/10.3892/ijo.25.6.1521