title: Maillard reaction products modulating the growth of human tumor cells in vitro.
abstract: We investigated the effect of a series of Maillard reaction products formed from carbohydrates under household heating conditions on the growth of human tumor cells in vitro. 4-Hydroxy-5-methyl-3-(2H)-furanone (1) was found to potently enhance the proliferation of human tumor cells. In contrast, the Maillard-type chromophores 2-(2-furyl)methylidene-4-hydroxy-5-methyl-2H-furan-3-one (2), 4-(2-furyl)-7-[(2-furyl)methylidene]-2-hydroxy-2H,7H,8aH-pyrano[2,3-b]- pyran-3-one (6), and 3-hydroxy-4[(E)-(2-furyl)methylidene]methyl-3-cyclopentene-1,2 dione (13) inhibited the growth of human tumor cells in vitro in the low micromolar range. GXF251L cells (gastric carcinoma), synchronized by serum deprivation, were retained in the G1-phase of the cell cycle after treatment with 2, 6, or 13 for 24 h. Concomitantly, a distinct sub-G1 peak was observed, indicative for apoptosis induction. DNA fragmentation was further investigated by ELISA using antibodies raised against histones and DNA. 2 induced a significant increase of fragmented DNA at concentrations > or = 30 microM. After treatment with compound 6, DNA fragmentation was observed at a higher concentration range (> or = 50 microM), whereas incubation with 13 resulted in a marked DNA fragmentation already at 20 microM. On the protein level, the activation of caspase 3, as an early marker for apoptosis induction, was determined. The results were almost identical to those obtained in the DNA fragmentation ELISA. In summary, Maillard reaction products potently modulating the growth of human tumor cells were identified. The Maillard-type chromophores 2, 6, and 13 were found to interfere with the proliferation of gastric carcinoma cells, causing cell cycle arrest and apoptosis induction.
authors.affiliation: Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern Erwin-Schroedinger-Strasse 52, 67663 Kaiserslautern, Germany. marko@rhrk.uni-kl.de
authors.forename: Doris
authors.initials: D
authors.lastname: Marko
authors.forename: Michael
authors.initials: M
authors.lastname: Habermeyer
authors.forename: Monika
authors.initials: M
authors.lastname: Kemény
authors.forename: Ulrike
authors.initials: U
authors.lastname: Weyand
authors.forename: Ellen
authors.initials: E
authors.lastname: Niederberger
authors.forename: Oliver
authors.initials: O
authors.lastname: Frank
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005562:Formazans / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D015416:Maillard Reaction; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013778:Tetrazolium Salts / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: C444300:3-hydroxy-4-(-(2-furyl)methylidene)methyl-3-cyclopentene-1,2-dione; D000970:Antineoplastic Agents; D003517:Cyclopentanes; D005562:Formazans; D005663:Furans; D013778:Tetrazolium Salts; C079782:MTT formazan; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C113254:4-hydroxy-5-methyl-3(2H)-furanone