Rapid inhibition of ongoing DNA synthesis in human glioma tissue by genistein

  • Authors:
    • Juan Sebastian Yakisich
    • Ingrid Ohlsson Lindblom
    • Åke Siden
    • Mabel H. Cruz
  • View Affiliations

  • Published online on: September 1, 2009     https://doi.org/10.3892/or_00000473
  • Pages: 569-574
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Abstract

The effect of genistein, a protein tyrosine kinase and topoisomerase II inhibitor, on the DNA synthesis rate was studied in 21 human glioma specimens obtained at routine craniotomies for tumor resection. Ongoing DNA synthesis rate was determined by using a method based on the generation of tissue mini-units immediately after tumor resection and short incubation time (0-120 min) with [methyl-3H]-thymidine. A 9-77% inhibition of DNA synthesis rate by 100 µM genistein was observed in 18/21 of the glioma specimens. In these cases, the average percentage of inhibition was 55±20% (mean ± SD, P<0.0001, Student's t-test) and the inhibitory effect was >50% in 12/18 of the cases. In 3 cases genistein increased the DNA synthesis rate. The inhibitory effect of genistein had a short-time onset and was concentration-dependent. Additional experiments in 4 cases showed that herbimycin A had no effect on DNA synthesis rate while etoposide inhibited similarly to that of genistein. Our results suggest that the effect of genistein on DNA synthesis rate in gliomas is independent of protein kinase inhibition and probably mediated by topoisomerase II inhibition. In the RG2 model, 50 µM genistein inhibited ongoing DNA synthesis in glioma cells with little or no effect in normal tissue. The data also encourage further investigations on the therapeutic potential of genistein for gliomas.

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September 2009
Volume 22 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yakisich JS, Ohlsson Lindblom I, Siden Å and Cruz MH: Rapid inhibition of ongoing DNA synthesis in human glioma tissue by genistein. Oncol Rep 22: 569-574, 2009.
APA
Yakisich, J.S., Ohlsson Lindblom, I., Siden, Å., & Cruz, M.H. (2009). Rapid inhibition of ongoing DNA synthesis in human glioma tissue by genistein. Oncology Reports, 22, 569-574. https://doi.org/10.3892/or_00000473
MLA
Yakisich, J. S., Ohlsson Lindblom, I., Siden, Å., Cruz, M. H."Rapid inhibition of ongoing DNA synthesis in human glioma tissue by genistein". Oncology Reports 22.3 (2009): 569-574.
Chicago
Yakisich, J. S., Ohlsson Lindblom, I., Siden, Å., Cruz, M. H."Rapid inhibition of ongoing DNA synthesis in human glioma tissue by genistein". Oncology Reports 22, no. 3 (2009): 569-574. https://doi.org/10.3892/or_00000473