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-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 (ROSin), and notably inhibited 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-decreasing agents are suggested.
Nagao
N
N
Department of Cell Biochemistry, Hiroshima Prefectural University School of BioSciences, Shobara, Japan.
Nakayama
T
T
Etoh
T
T
Saiki
I
I
Miwa
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy / Q000517:prevention & control / Q000556:secondary; D016166:Free Radical Scavengers; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C011669:ascorbate-2-phosphate; D001205:Ascorbic Acid