GL15 and U251 glioblastoma-derived human cell lines are peculiarly susceptible to induction of mitotic death by very low concentrations of okadaic acid

  • Authors:
    • Emilia Castigli
    • Miriam Sciaccaluga
    • Gianluca Schiavoni
    • Flora Brozzi
    • Roberto Fabiani
    • Paolo Gorello
    • Gian Luigi Gianfranceschi
  • View Affiliations

  • Published online on: February 1, 2006     https://doi.org/10.3892/or.15.2.463
  • Pages: 463-470
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Abstract

The challenging possibility of selectively inducing mitotic death in tumor cells by combining genotoxic agents with the inhibition of G2 checkpoints of the cell cycle is the subject of intensive investigation. We show that very low concentrations (3.5 and 5 nM) of okadaic acid induce mitotic death in two glioblastoma cell lines, in the absence of genotoxic agents. At the concentrations used, the main target of okadaic acid action is protein phosphatase 2A (PP2A), an enzyme deeply involved in the negative control of cell-cycle progression. The peculiar susceptibility of glioblastoma cells to induction of mitotic death by very low concentrations of okadaic acid must be related to an impairment of PP2A activity and to a specific deficiency in some cell-cycle checkpoints. In addition to its ability to induce abnormal mitoses in actively proliferating glioblastoma cells, okadaic acid possesses the ability to force semi-confluent glioblastoma cells to the M phase of the cell cycle, where they show the same abnormalities observed in actively proliferating glioblastoma cells. In semi-confluent cells the induction of mitotic death involves the activity of both the extracellular signal regulated kinases (ERKs) and the M-phase promoting factor: okadaic acid overstimulates ERK activity, and PD98059 (inhibitor of ERK activation) as well as roscovitine (S)-isomer (specific inhibitor of M-phase promoting factor activity) counteract the induction of mitotic death. Our results show that, without the use of genotoxic agents, it is possible to induce mitotic death in glioblastoma cells by activating the same uncontrolled pathways responsible for the uncontrolled proliferation.

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February 2006
Volume 15 Issue 2

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

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Spandidos Publications style
Castigli E, Sciaccaluga M, Schiavoni G, Brozzi F, Fabiani R, Gorello P and Gianfranceschi GL: GL15 and U251 glioblastoma-derived human cell lines are peculiarly susceptible to induction of mitotic death by very low concentrations of okadaic acid. Oncol Rep 15: 463-470, 2006
APA
Castigli, E., Sciaccaluga, M., Schiavoni, G., Brozzi, F., Fabiani, R., Gorello, P., & Gianfranceschi, G.L. (2006). GL15 and U251 glioblastoma-derived human cell lines are peculiarly susceptible to induction of mitotic death by very low concentrations of okadaic acid. Oncology Reports, 15, 463-470. https://doi.org/10.3892/or.15.2.463
MLA
Castigli, E., Sciaccaluga, M., Schiavoni, G., Brozzi, F., Fabiani, R., Gorello, P., Gianfranceschi, G. L."GL15 and U251 glioblastoma-derived human cell lines are peculiarly susceptible to induction of mitotic death by very low concentrations of okadaic acid". Oncology Reports 15.2 (2006): 463-470.
Chicago
Castigli, E., Sciaccaluga, M., Schiavoni, G., Brozzi, F., Fabiani, R., Gorello, P., Gianfranceschi, G. L."GL15 and U251 glioblastoma-derived human cell lines are peculiarly susceptible to induction of mitotic death by very low concentrations of okadaic acid". Oncology Reports 15, no. 2 (2006): 463-470. https://doi.org/10.3892/or.15.2.463