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


CONCLUSIONS
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.
Simoens
Cindy
C
Laboratory of Cancer Research and Clinical Oncology, Department of Medical Oncology, University of Antwerp (UA/UZA), Wilrijk (Antwerp), Belgium. cindy.simoens@ua.ac.be
Lardon
Filip
F
Pauwels
Bea
B
De Pooter
Christel M J
CM
Lambrechts
Hilde A J
HA
Pattyn
Greet G O
GG
Breillout
Fabienne
F
Vermorken
Jan B
JB
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002277:Carcinoma / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005720:Gamma Rays; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008870:Microtubules / Q000187:drug effects; D015394:Molecular Structure; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014062:Tongue Neoplasms / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000473:pathology; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D011838:Radiation-Sensitizing Agents; C111217:vinflunine; D014747:Vinblastine; D000077235:Vinorelbine