We investigated the effect of a series of Maillard reaction products formed from carbohydratesunder household heating conditions on the growth of human tumor cells in vitro. 4-Hydroxy-5-methyl-3-(2
H)-furanone (
1) was found to potently enhance the proliferation of human tumorcells. In contrast, the Maillard-type chromophores 2-(2-furyl)methylidene-4-hydroxy-5-methyl-2
H-furan-3-one (
2), 4-(2-furyl)-7-[(2-furyl)methylidene]-2-hydroxy-2
H,7
H,8a
H-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. GXF251Lcells (
gastric carcinoma), synchronized by serum deprivation, were retained in the G
1-phaseof the cell cycle after treatment with
2,
6, or
13 for 24 h. Concomitantly, a distinct sub-G
1peak was observed, indicative for apoptosis induction. DNA fragmentation was furtherinvestigated by ELISA using antibodies raised against histones and DNA.
2 induced asignificant increase of fragmented DNA at concentrations
![](/images/entities/ge.gif)
30
![](/images/entities/mgr.gif)
M. After treatment withcompound
6, DNA fragmentation was observed at a higher concentration range (
![](/images/entities/ge.gif)
50
![](/images/entities/mgr.gif)
M),whereas incubation with
13 resulted in a marked DNA fragmentation already at 20
![](/images/entities/mgr.gif)
M. Onthe protein level, the activation of caspase 3, as an
early marker for apoptosis induction, wasdetermined. The results were almost identical to those obtained in the DNA fragmentationELISA. In summary, Maillard reaction products potently modulating the growth of humantumor cells were identified. The Maillard-type chromophores
2,
6, and
13 were found to interferewith the proliferation of
gastric carcinoma cells, causing cell cycle arrest and apoptosisinduction.