title: Pharmacologic concentrations of ascorbate are achieved by parenteral administration and exhibit antitumoral effects.
abstract: Recently, it has been proposed that pharmacologic concentrations of ascorbate (vitamin C) can be reached by intravenous injection. Because high doses of ascorbate have been described to possess anticancer effects, the therapeutic potential of these concentrations has been studied, both in vitro and in vivo. By using 2-h exposures, a protocol that mimics a parenteral use, we observed that pharmacologic concentrations of ascorbate killed various cancer cell lines very efficiently (EC(50) ranging from 3 to 7 mM). The mechanism of cytotoxicity is based on the production of extracellular hydrogen peroxide and involves intracellular transition metals. In agreement with what has been previously published, our in vivo results show that both intravenous and intraperitoneal administration of ascorbate induced pharmacologic concentrations (up to 20 mM) in blood. In contrast, the concentrations reached orally remained physiological. According to pharmacokinetic data, parenteral administration of ascorbate decreased the growth rate of a murine hepatoma, whereas oral administration of the same dosage did not. We also report that pharmacologic concentrations of ascorbate did not interfere with but rather reinforced the activity of five important chemotherapeutic drugs. Taken together, these results confirm that oral and parenteral administration of ascorbate are not comparable, the latter resulting in pharmacologic concentrations of ascorbate that exhibit interesting anticancer properties.
authors.affiliation: PMNT Unit, Louvain Drug Research Institute, Université Catholique de Louvain, 1200 Bruxelles, Belgium.
authors.forename: Julien
authors.initials: J
authors.lastname: Verrax
authors.forename: Pedro Buc
authors.initials: PB
authors.lastname: Calderon
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D054796:Drug Dosage Calculations; D004357:Drug Synergism; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007263:Infusions, Parenteral; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051379:Mice
chemical_list: D016166:Free Radical Scavengers; D002374:Catalase; D001205:Ascorbic Acid; D000111:Acetylcysteine