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

<p>Abstract</p> <p>Background</p> <p>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 radiosensitising and cell cycle effects.</p> <p>Methods</p> <p>Four human tumour cell lines were tested under identical experimental conditions, using equitoxic concentrations of vinflunine and vinorelbine.</p> <p>Results</p> <p>Vinflunine and vinorelbine induced a comparable radiosensitising 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.</p> <p>Conclusion</p> <p>The radiosensitising 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 radiosensitising effects. Considering the more favourable toxicity profile of vinflunine, this agent might be more promising than vinorelbine for chemoradiation studies in the clinic.</p

Effet de la 5'-isobutylthioadenosine et d'une depletion en methionine sur la proliferation tumorale in vitro et la dissemination metastatique de tumeurs in vivo

SIGLECNRS T 58791 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

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

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&nbsp;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&nbsp;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&nbsp;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&nbsp;potential.</p

Comparative study of the radiosensitising and cell cycle effects of vinflunine and vinorelbine, -3

during 4, 24 and 48 hours and 24 and 48 h after drug removal. FL-2A = DNA content. Events = number of fluorescent nuclei.<p><b>Copyright information:</b></p><p>Taken from "Comparative study of the radiosensitising and cell cycle effects of vinflunine and vinorelbine, "</p><p>http://www.biomedcentral.com/1471-2407/8/65</p><p>BMC Cancer 2008;8():65-65.</p><p>Published online 29 Feb 2008</p><p>PMCID:PMC2311317.</p><p></p

Comparative study of the radiosensitising and cell cycle effects of vinflunine and vinorelbine, -1

Ne during 4, 24 and 48 hours and 24 and 48 h after drug removal. FL-2A = DNA content. Events = number of fluorescent nuclei.<p><b>Copyright information:</b></p><p>Taken from "Comparative study of the radiosensitising and cell cycle effects of vinflunine and vinorelbine, "</p><p>http://www.biomedcentral.com/1471-2407/8/65</p><p>BMC Cancer 2008;8():65-65.</p><p>Published online 29 Feb 2008</p><p>PMCID:PMC2311317.</p><p></p

Comparative study of the radiosensitising and cell cycle effects of vinflunine and vinorelbine, -2

E during 4, 24 and 48 hours and 24 and 48 h after drug removal. FL-2A = DNA content. Events = number of fluorescent nuclei.<p><b>Copyright information:</b></p><p>Taken from "Comparative study of the radiosensitising and cell cycle effects of vinflunine and vinorelbine, "</p><p>http://www.biomedcentral.com/1471-2407/8/65</p><p>BMC Cancer 2008;8():65-65.</p><p>Published online 29 Feb 2008</p><p>PMCID:PMC2311317.</p><p></p