title: Anti-metastatic effect of an autooxidation-resistant and lipophilic ascorbic acid derivative through inhibition of tumor invasion.
abstract: The invasion of human fibrosarcoma HT-1080 cells through Matrigel was shown to be inhibited by pretreatment with ascorbic acid (Asc) or its four derivatives, such as Asc-6-O-palmitate (Asc6Plm), Asc-2-O-phosphate (Asc2P), Asc-2-O-phosphate-6-O-palmitate (Asc2P6Plm), and Asc-5,6-benzylidene (Asc5,6Bz) of non-cytotoxic concentrations for 1 or 18 hr. Two lipophilic derivatives such as Asc6Plm and Asc2P6Plm exerted an invasiveness-inhibitory activity more markedly with 1-hr pretreatment, being a more practical index in terms of the plasma half-life, than Asc, Asc5,6Bz or Asc2P being less lipophilic. Considerably less cytotoxicity (a > 3.3-fold higher IC50 for 1-hr pretreatment) of Asc2P6Plm sufficiently compensated a slightly lower invasiveness-inhibitory activity (a < 1.8-fold higher EC50) as compared with Asc6Plm. Pulmonary metastasis of mouse melanoma B16BL6 cells injected into the tail vein was also inhibited by intravenous administration with Asc2P6Plm dose-dependently. Thus Asc2P6Plm, a lipophilicity-hydrophilicity balanced molecule protectively blockd in the autooxidation-prone moiety, is anticipated as a potent anti-metastatic agent via inhibition of tumor invasion.
authors.affiliation: Department of Cell Biochemistry, Hiroshima Prefectural University School of BioSciences, Japan.
authors.forename: J W
authors.initials: JW
authors.lastname: Liu
authors.forename: N
authors.initials: N
authors.lastname: Nagao
authors.forename: K
authors.initials: K
authors.lastname: Kageyama
authors.forename: N
authors.initials: N
authors.lastname: Miwa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001597:Benzylidene Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003094:Collagen; D004338:Drug Combinations; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology*; D006207:Half-Life; D007797:Laminin; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D008546:Melanoma, Experimental / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D011509:Proteoglycans; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000637:transplantation
chemical_list: C403966:6-O-palmitol-ascorbate-2-O-phosphate; D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; C011669:ascorbate-2-phosphate; D003094:Collagen; D001205:Ascorbic Acid; C031226:6-O-palmitoylascorbic acid; C070680:zilascorb