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: J W Liu, N Nagao, K Kageyama, N Miwa
• Journal: Anticancer research (Anticancer Res) 2000 Jan-Feb Vol. 20 Issue 1A Pg. 113-8 ISSN: 0250-7005 [Print] Greece
• PMID: 10769642 (Publication Type: Comparative Study, Journal Article)

Chemical References

• 6-O-palmitol-ascorbate-2-O-phosphate
• Antineoplastic Agents
• Benzylidene Compounds
• Drug Combinations
• Laminin
• Proteoglycans
• matrigel
• ascorbate-2-phosphate
• Collagen
• Ascorbic Acid
• 6-O-palmitoylascorbic acid
• zilascorb

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Ascorbic Acid (analogs & derivatives, chemistry, pharmacology, therapeutic use)
• Benzylidene Compounds (chemistry, pharmacology, therapeutic use)
• Cell Survival
• Chemical Phenomena
• Chemistry, Physical
• Collagen
• Drug Combinations
• Female
• Fibrosarcoma (pathology)
• Half-Life
• Laminin
• Lung Neoplasms (prevention & control, secondary)
• Melanoma, Experimental (prevention & control, secondary)
• Mice
• Mice, Inbred C57BL
• Molecular Structure
• Neoplasm Invasiveness (prevention & control)
• Proteoglycans
• Structure-Activity Relationship
• Tumor Cells, Cultured (drug effects, transplantation)