title: Anti-cancer effect of pharmacologic ascorbate and its interaction with supplementary parenteral glutathione in preclinical cancer models.
abstract: Two popular complementary, alternative, and integrative medicine therapies, high-dose intravenous ascorbic acid (AA) and intravenous glutathione (GSH), are often coadministered to cancer patients with unclear efficacy and drug-drug interaction. In this study we provide the first survey evidence for clinical use of iv GSH with iv AA. To address questions of efficacy and drug-drug interaction, we tested 10 cancer cell lines with AA, GSH, and their combination. The results showed that pharmacologic AA induced cytotoxicity in all tested cancer cells, with IC(50) less than 4 mM, a concentration easily achievable in humans. GSH reduced cytotoxicity by 10-95% by attenuating AA-induced H(2)O(2) production. Treatment in mouse pancreatic cancer xenografts showed that intraperitoneal AA at 4 g/kg daily reduced tumor volume by 42%. Addition of intraperitoneal GSH inhibited the AA-induced tumor volume reduction. Although all treatments (AA, GSH, and AA+GSH) improved survival rate, AA+GSH inhibited the cytotoxic effect of AA alone and failed to provide further survival benefit. These data confirm the pro-oxidative anti-cancer mechanism of pharmacologic AA and suggest that AA and GSH administered together provide no additional benefit compared with AA alone. There is an antagonism between ascorbate and glutathione in treating cancer, and therefore iv AA and iv GSH should not be coadministered to cancer patients on the same day.
authors.affiliation: Program in Integrative Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stone
authors.forename: Garrett
authors.initials: G
authors.lastname: Sullivan
authors.forename: Jeanne A
authors.initials: JA
authors.lastname: Drisko
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D005260:Female; D005978:Glutathione / Q000008:administration & dosage / Q000009:adverse effects; D006367:HeLa Cells; D006801:Humans; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000975:Antioxidants; D005978:Glutathione; D001205:Ascorbic Acid