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Further mechanistic unravelling of the influence of the cell cycle effects on the radiosensitising mechanism of vinflunine, in vitro

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Abstract

Purpose

Vinflunine is an innovative microtubule inhibitor belonging to the vinca alkaloid class that possesses radiosensitising properties, which could lead to promising activity in chemoradiation studies in the clinic.

Method

In the current study, different incubation times with vinflunine, immediately before radiation and different time intervals between vinflunine treatment and radiation were investigated, in vitro, using four different human tumour cell lines differing in cell type and p53 status. Results were correlated with the cell cycle distribution at the moment of radiation, in order to elucidate the role of cell cycle perturbations caused by vinflunine on its radiosensitising effect.

Results

Radiosensitisation was observed in all cell lines, and maximal radiosensitisation was both cell line- and schedule-dependent. The cell cycle distributions were cell line-dependent also, and when correlated with the observed radiosensitising effects could explain many (but not all) of the radiosensitising properties of vinflunine.

Conclusion

The cell cycle perturbations caused by vinflunine may definitely have an impact on its radiosensitising potential, but other factors must play a role because of some unaccountable differences between cell cycle distribution and the radiosensitising potential.

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Acknowledgments

We would like to thank Dr. Christel De Pooter from the Radiotherapy department of the Sint-Augustinus Hospital Antwerp for giving us the opportunity to irradiate our cells. This study was financially supported by a grant from the Emmanuel van der Schueren Foundation.

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Authors and Affiliations

  1. Laboratory of Cancer Research and Clinical Oncology, Department of Medical Oncology, University of Antwerp (UA/UZA), Universiteitsplein 1, 2610, Wilrijk (Antwerp), Belgium

    Cindy Simoens, Bea Pauwels, Jan B. Vermorken, Greet G. O. Pattyn, Hilde A. J. Lambrechts & Filip Lardon

  2. Centre de Développement Oncologie, Institut de Recherche Pierre Fabre, 45, Place Abel Gance, 92654, Boulogne Cedex, France

    Fabienne Breillout

Authors
  1. Cindy Simoens
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  2. Bea Pauwels
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  3. Jan B. Vermorken
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  4. Greet G. O. Pattyn
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  5. Hilde A. J. Lambrechts
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  6. Fabienne Breillout
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  7. Filip Lardon
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Correspondence to Cindy Simoens.

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Simoens, C., Pauwels, B., Vermorken, J.B. et al. Further mechanistic unravelling of the influence of the cell cycle effects on the radiosensitising mechanism of vinflunine, in vitro. Cancer Chemother Pharmacol 62, 183–193 (2008). https://doi.org/10.1007/s00280-007-0587-4

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  • DOI: https://doi.org/10.1007/s00280-007-0587-4

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