Tumor invasion is inhibited by phosphorylated ascorbate via enrichment of intracellular vitamin C and decreasing of oxidative stress

Tumor metastasis and invasion were shown to be inhibited by the 2-O-phospho rylated form (Asc2P) of L-ascorbic acid (Asc); intact Asc did not inhibit t umor invasion when added once, but appreciably inhibited it upon repeated a ddition. The anti-metastatic effect is attributable to a marked enrichment of intracellular Asc by Asc2P, subsequently dephosphorylated. Asc2P scaveng ed most of the intracellular reactive oxygen species (ROSin), and notably i nhibited production of matrix metalloproteases and cell motility. ROSin was decreased by Asc2P more markedly than by Asc added once. Thus, involvement of ROSin in tumor invasion and a potent anti-metastatic therapy by ROSin-d ecreasing agents are suggested.