title: 5-Fluorouracil cytotoxicity in human colon HT-29 cells with moderately increased or decreased cellular glutathione level.
abstract: Little is known whether diet or certain components in the diet can modulate the efficacy of 5-fluorouracil (5FU) in patients with colon carcinoma. Glutathione (GSH), an important antioxidant and anticarcinogen, is present in many foods in varying amounts. This study examined whether a moderately increased or decreased cellular GSH level had any effect on the growth of human colon adenocarcinoma cells HT-29 and on the cytotoxic activity of 5FU in these cells. GSH and buthionine sulfoximine were used to enhance or reduce the GSH level respectively in these cells. A 34% increase in cellular GSH level had no effect on the growth of HT-29 cells, nor on the cytotoxic activity of 5FU as determined by the MTT colorimetric assay and cell counts. A 50% reduction in the cellular GSH level was found to enhance 5FU cytotoxicity by 20% to 31% as determined by the MTT colorimetric assay, depending on the 5FU concentration. This study shows that a moderate change in the GSH level in HT-29 cells had little or no effect on the cells' growth, but a decrease in cellular GSH level slightly enhanced the cytotoxic activity of 5FU in these cells.
authors.affiliation: Department of Internal Medicine, University of South Florida College of Medicine, Tampa 33612-4799, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Chen
authors.forename: L T
authors.initials: LT
authors.lastname: Chen
authors.forename: H W
authors.initials: HW
authors.lastname: Boyce
mesh_terms: D000230:Adenocarcinoma; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003110:Colonic Neoplasms; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D005472:Fluorouracil