[Study on the mechanism of inhibition of tumor cell motility by ascorbic acid derivatives].

Our previous study shows that tumor invasion is inhibited by 2-O-phosphorylated ascorbate-6-O-palmitylester (Asc2P6Plm). In the present study, the mechanism underlying the inhibitory effect of Asc2P6Plm on invasion of human fibrosarcoma cells HT-1080 was attempted to be analysed. Migratory ability of the tumor cells was shown to be inhibited in a dose-dependent manner by treatment with Asc2P6Plm at 50-300 micromol/L for 1 hr. Hydroxyl radicals in homogenates of Asc2P6Plm-treated HT-1080 cells were markedly diminished relative to those of non-treated cells as evaluated by electron spin resonance method using the spin-trapping agent DMPO. F-actin was localized in the vicinity of the cell membrane abundantly in nontreated cells, but was diminished in a time-dependent manner in Asc2P6Plm-treated cells as shown with the F-actin-directed agent NBD-phallacidin. The cell adhesion-controlling molecule RhoA increased time-dependently in the cell nucleus of Asc2P6Plm-treated cells as shown by Western blots. Thus the inhibition of tumor invasion by Asc2P6Plm was shown to be attributed to decreases in both the cell migratory ability and the F-actin localization near the cell membrane, which may result from an increase in RhoA in the cell nucleus and reduction of intracellular ROS that is achieved by enrichment of intracellular Asc derived from Asc2P6Plm.