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01-08-2006 | Original Article

Cell cycle effects of vinflunine, the most recent promising Vinca alkaloid, and its interaction with radiation, in vitro

Authors: Cindy Simoens, Jan B. Vermorken, Annelies E. C. Korst, Bea Pauwels, Christel M. J. De Pooter, Greet G. O. Pattyn, Hilde A. J. Lambrechts, Fabienne Breillout, Filip Lardon

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2006

Abstract

Purpose: Vinflunine (VFL) is a novel third generation Vinca alkaloid with superior antitumour activity in preclinical models and an anticipated more favourable toxicity profile compared to the other Vinca alkaloids. Method: We investigate the radiosensitising properties of VFL and its cell cycle effects in four human tumour cell lines (ECV304, MCF-7, H292, and CAL-27). The sulforhodamine B test was used to determine cell survival, and cell cycle analysis was performed by flow cytometry. Radiosensitisation (RS) was represented by dose enhancement factors (DEFs). Results: Twenty-four hours treatment with VFL before radiation caused dose-dependent RS in all cell lines. This was most pronounced in ECV304 cells with RS already at VFL concentrations that reduced cell survival by 10% (IC10). DEFs ranged from 1.57 to 2.29 in the different cell lines. A concentration-dependent G2/M block was observed (starting at 4 h of incubation). After maximal G2/M blockade cells started cycling again, mainly by mitosis, while a small portion of cells started a polyploid cell cycle. Also drug removal immediately caused recycling of cells and induction of a polyploid cell population. The polyploid cell population was most impressively noticeable after prolonged incubation with VFL (48 h), in particular in CAL-27 and ECV304. This was never observed in a tested normal fibroblast cell line (Fi 360). The fate of these cells is of particular interest, but yet uncertain. Conclusion: VFL has radiosensitising potential. The exact role of the cell cycle effects of VFL in its radiosensitising mechanism is still not fully elucidated and requires further study.

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Title: Cell cycle effects of vinflunine, the most recent promising Vinca alkaloid, and its interaction with radiation, in vitro
Authors: Cindy Simoens
Jan B. Vermorken
Annelies E. C. Korst
Bea Pauwels
Christel M. J. De Pooter
Greet G. O. Pattyn
Hilde A. J. Lambrechts
Fabienne Breillout
Filip Lardon
Publication date: 01-08-2006
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 2/2006
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-005-0147-8

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