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Comparative study of the radiosensitizing and cell cycle effects of vinflunine and vinorelbine, in vitro.

Simoens C, Lardon F, Pauwels B, De Pooter CM, Lambrechts HA, Pattyn GG, Breillout F, Vermorken JB - BMC Cancer (2008)

Bottom Line: Regarding the cell cycle effects, a statistically significant concentration-dependent G2/M block was seen after 24 h incubation with vinorelbine in all tested cell lines.Similar results, with small cell line-related differences, were observed with vinflunine.The cell cycle effects could be related to the observed radiosensitizing effects.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Cancer Research and Clinical Oncology, Department of Medical Oncology, University of Antwerp (UA/UZA), Wilrijk (Antwerp), Belgium. cindy.simoens@ua.ac.be

ABSTRACT

Background: Vinca alkaloids are an important class of anticancer agents and semisynthetic vinca alkaloids are developed to improve the therapeutic index of this class of drugs. In the present study, a direct comparison was made between vinflunine and vinorelbine regarding their radiosensitizing and cell cycle effects.

Methods: Four human tumour cell lines were tested under identical experimental conditions, using equitoxic concentrations of vinflunine and vinorelbine.

Results: Vinflunine and vinorelbine induced a comparable radiosensitizing effect (p-value never below 0.01) when cells were incubated for 24 h immediately prior to radiation. Regarding the cell cycle effects, a statistically significant concentration-dependent G2/M block was seen after 24 h incubation with vinorelbine in all tested cell lines. Similar results, with small cell line-related differences, were observed with vinflunine.

Conclusion: The radiosensitizing effects of both semisynthetic vinca alkaloids were comparable (not statistically different) and nearly always cell line-specific and concentration-dependent. The cell cycle effects could be related to the observed radiosensitizing effects. Considering the more favourable toxicity profile of vinflunine, this agent might be more promising than vinorelbine for chemoradiation studies in the clinic.

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Related in: MedlinePlus

DNA histograms of vinorelbine and vinflunine in ECV304 cells. detailed legend: DNA histograms of ECV304 cells treated with equitoxic concentrations of vinorelbine or vinflunine during 4, 24 and 48 hours and 24 and 48 h after drug removal. FL-2A = DNA content. Events = number of fluorescent nuclei.
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Figure 1: DNA histograms of vinorelbine and vinflunine in ECV304 cells. detailed legend: DNA histograms of ECV304 cells treated with equitoxic concentrations of vinorelbine or vinflunine during 4, 24 and 48 hours and 24 and 48 h after drug removal. FL-2A = DNA content. Events = number of fluorescent nuclei.

Mentions: Figures 1, 2, 3, 4 show representative DNA-histograms of all tested cell lines after different time points of exposure to VRL or VFL, and at different time points after drug removal.


Comparative study of the radiosensitizing and cell cycle effects of vinflunine and vinorelbine, in vitro.

Simoens C, Lardon F, Pauwels B, De Pooter CM, Lambrechts HA, Pattyn GG, Breillout F, Vermorken JB - BMC Cancer (2008)

DNA histograms of vinorelbine and vinflunine in ECV304 cells. detailed legend: DNA histograms of ECV304 cells treated with equitoxic concentrations of vinorelbine or vinflunine during 4, 24 and 48 hours and 24 and 48 h after drug removal. FL-2A = DNA content. Events = number of fluorescent nuclei.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2311317&req=5

Figure 1: DNA histograms of vinorelbine and vinflunine in ECV304 cells. detailed legend: DNA histograms of ECV304 cells treated with equitoxic concentrations of vinorelbine or vinflunine during 4, 24 and 48 hours and 24 and 48 h after drug removal. FL-2A = DNA content. Events = number of fluorescent nuclei.
Mentions: Figures 1, 2, 3, 4 show representative DNA-histograms of all tested cell lines after different time points of exposure to VRL or VFL, and at different time points after drug removal.

Bottom Line: Regarding the cell cycle effects, a statistically significant concentration-dependent G2/M block was seen after 24 h incubation with vinorelbine in all tested cell lines.Similar results, with small cell line-related differences, were observed with vinflunine.The cell cycle effects could be related to the observed radiosensitizing effects.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Cancer Research and Clinical Oncology, Department of Medical Oncology, University of Antwerp (UA/UZA), Wilrijk (Antwerp), Belgium. cindy.simoens@ua.ac.be

ABSTRACT

Background: Vinca alkaloids are an important class of anticancer agents and semisynthetic vinca alkaloids are developed to improve the therapeutic index of this class of drugs. In the present study, a direct comparison was made between vinflunine and vinorelbine regarding their radiosensitizing and cell cycle effects.

Methods: Four human tumour cell lines were tested under identical experimental conditions, using equitoxic concentrations of vinflunine and vinorelbine.

Results: Vinflunine and vinorelbine induced a comparable radiosensitizing effect (p-value never below 0.01) when cells were incubated for 24 h immediately prior to radiation. Regarding the cell cycle effects, a statistically significant concentration-dependent G2/M block was seen after 24 h incubation with vinorelbine in all tested cell lines. Similar results, with small cell line-related differences, were observed with vinflunine.

Conclusion: The radiosensitizing effects of both semisynthetic vinca alkaloids were comparable (not statistically different) and nearly always cell line-specific and concentration-dependent. The cell cycle effects could be related to the observed radiosensitizing effects. Considering the more favourable toxicity profile of vinflunine, this agent might be more promising than vinorelbine for chemoradiation studies in the clinic.

Show MeSH
Related in: MedlinePlus