Maillard reaction products modulating the growth of human tumor cells in vitro.
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.
Marko
Doris
D
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
Habermeyer
Michael
M
Kemény
Monika
M
Weyand
Ulrike
U
Niederberger
Ellen
E
Frank
Oliver
O
Hofmann
Thomas
T
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
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