Effect of microtubule-targeting drugs on cell-cell and cell-matrix junctions in tumor epithelial cells.

In this study, we investigated the effects of microtubule-targeting drugs, which either destabilize (the Vinca alkaloid vincristine) or stabilize (the taxane derivative docetaxel) microtubules, on the cell-cell and cell-matrix adhesive junctions of Caco-2 tumor epithelial cells, using fluorescence imaging and functional assays. We found that, in sub-confluent (but not confluent) cells, vincristine (but not docetaxel) affected cell-cell junction morphology. Furthermore, docetaxel (but not vincristine) attenuated the formation of the peri-junctional actomyosin ring and enhanced the internalization of junctional adhesion molecule-A.

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.

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 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 effect.

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

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.