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


METHODS
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.


CONCLUSIONS
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.
Simoens
Cindy
C
Laboratory of Cancer Research and Clinical Oncology, Department of Medical Oncology, University of Antwerp, 2610 Wilrijk, Belgium. cindy.simoens@ua.ac.be
Vermorken
Jan B
JB
Korst
Annelies E C
AE
Pauwels
Bea
B
De Pooter
Christel M J
CM
Pattyn
Greet G O
GG
Lambrechts
Hilde A J
HA
Breillout
Fabienne
F
Lardon
Filip
F
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D011839:Radiation, Ionizing; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; C111217:vinflunine; D014747:Vinblastine