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

Abstract

Tumor metastasis and invasion were shown to be inhibited by the 2-O-phosphorylated form (Asc2P) of l-ascorbic acid (Asc); intact Asc did not inhibit tumor invasion when added once, but appreciably inhibited it upon repeated addition. The anti-metastatic effect is attributable to a marked enrichment of intracellular Asc by Asc2P, subsequently dephosphorylated. Asc2P scavenged most of the intracellular reactive oxygen species (ROS_in), and notably inhibited production of matrix metalloproteases and cell motility. ROS_in was decreased by Asc2P more markedly than by Asc added once. Thus, involvement of ROS_in in tumor invasion and a potent anti-metastatic therapy by ROS_in-decreasing agents are suggested.