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.

Melanoidins produced by the Maillard reaction: Structure and biological activity

“…Synthesised and purified chromophoric MRPs, identified in thermal food processing products, were reported to inhibit the growth of human carcinoma cells in vitro by interfering with the proliferation of gastric carcinoma cells, causing cell cycle arrest and apoptosis (Marko et al, 2003). These results suggest that some melanoidins may inhibit the growth of human tumour cells.…”

“…During the intermediate stages, a-dicarbonyls, aldehydes, furaldehydes and furanone, are generated, which rapidly react with each other in an aldol-type condensation. Also, degradation of aldose sugars leads to the formation of furaldehydes and furanones too, such as furan-2-carboxaldehyde and furan-2-aldehyde (Marko et al, 2003;Shirahashi et al, 2009). A range of reactions takes place in the advanced stages of the MR, including cyclisations, dehydrations, retro-adolisations, rearrangements, isomerisations and additional condensations.…”

Five years of research on health risks and benefits of Maillard reaction products: An update

“…Another in vitro study reported an inhibition of tumor cell growth and microtubule assembly by chemically characterized MRPs formed from carbohydrates under household heating conditions [44]. Herein, the Maillard-type chromophores 2-(2-furyl)methylidene-4-hydroxy-5-methyl-2H-furan-3-one, 4- Heat-treated foods have played an important role in human nutrition since Homo habilis began to use fire [45].…”

Chemical properties and reactive oxygen and nitrogen species quenching activities of dry sugar–amino acid maillard reaction mixtures exposed to baking temperatures

“…These findings accompany the more established positive and negative effects of MRPs reported on food sensory and nutritional quality, respectively (Waller & Feather, 1983). Some bioactive properties for MRPs include both pro-and anti-oxidant activities (Cai et al, 2002;Chen & Kitts, 2008a;Kitts, Chen, & Jing, 2012), carcinogenesis (Skog, Johansson, & Jägerstad, 1998) or anti-cancer activity (Marko et al, 2003), genotoxicity and mutagenicity (Glösl et al, 2004;Kitts, Wu, Stich, & Powrie, 1993), and pro-and antiinflammatory activities (Chen & Kitts, 2011b;Muscat et al, 2007).…”