Apple Polyphenols and Products Formed in the Gut Differently Inhibit Survival of Human Cell Lines Derived from Colon Adenoma (LT97) and Carcinoma (HT29)

Abstract

Colorectal tumor risks could be reduced by polyphenol-rich diets that inhibit cell growth. Here, apple polyphenols were studied for effects on the survival of colon adenoma (LT97) and carcinoma-derived (HT29) cell lines. Three apple extracts (AEs) from harvest years 2002-2004 were isolated (AE02, AE03, and AE04) and fermented in vitro with human fecal flora. Extracts and fermentation products were analyzed for polyphenols with HPLC. The cells were treated with AEs (0-850 microg/mL) or fermented AEs (F-AEs, 0-9%), and survival was measured by DNA staining. All AEs contained high amounts of polyphenols (311-534 mg/g) and reduced cell survival (in LT97 > HT29). AE03 was most potent, possibly because it contained more quercetin compounds. Fermentation of AEs resulted in an increase of short chain fatty acids, and polyphenols were degraded. The F-AEs were approximately 3-fold less bioactive than the corresponding AEs, pointing to a loss of chemoprotective properties through fermentation.

Effects of cinnamaldehyde and thymol on cytotoxicity, tight junction barrier resistance, and cyclooxygenase-1 and -2 expression in Caco-2 cells

“…Notably, the contacts with natural microbiota and mucosal immune system of the gut are absent, for example. When nutrients are ingested by an animal, they can be fermented by the intestinal microbiota, and the produced metabolites can have different effects on intestinal epithelial cells, as observed for dietary polyphenols in human diet (Veeriah et al, 2007). The concentrations of cinnamaldehyde and thymol in the ileal and caecal contents of chickens are 0.2% to 4% of that in the feed (Nurminen et al, unpublished Figure 3.…”

Apple Procyanidins Induced Vascular Relaxation in Isolated Rat Aorta through NO/cGMP Pathway in Combination with Hyperpolarization by Multiple K+Channel Activations

“…Superoxide dismutase (SOD, EC 1.15.1.1) was from Sigma-Aldrich (St. Louis, MO). Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylc acid), TEA (tetraethyl ammonium chloride) as a non-selective K þ channel inhibitor, ODQ (1-H- [1,2,4]oxadiazolo- [4,3]quinoxalin-1-one) as a soluble guanylyl cyclase (sGC) inhibitor, atropine as a muscarinic receptor antagonist, paxillin as a largeconductance Ca…”

“…In a series of studies by us regarding the functionality of apple (Malus pumila) procyanidins (AP), they have proved effective in preventing lifestyle-related diseases such as obesity, 1) as in other reports on their anti-cancer cell growth 2) and anti-tumor activity.…”

Apple polyphenols modulate expression of selected genes related to toxicological defence and stress response in human colon adenoma cells

“…42 This is in accordance with previous findings showing that AE modulated growth and survival of LT97 cells with EC 50 values of 650.9 lg/ml after 24-hr treatment. 22 In addition, AE influenced genes from the stress and signal transduction pathways namely, FMO1, GPX2, HSPA5 and UBE2D1, the products of which have several functions such as peroxidase activity and ubiquitination. 43 Moreover, there was an AE-mediated upregulation of the apoptosis mediator CASP10, which is part of the caspase cascade.…”

“…Prolonged treatment resulted in pronounced loss of numbers of cells compared to the medium control after 72 hr to 82 and 71%, respectively. 22 The effect of apple polyphenol extract on cell-cycle phases will be analyzed by flow cytometric methods and the results will be published in a later manuscript, together with data on modulation of apoptosis by the extract. In the present study, these 2 concentrations were used to test if there were any differences in biological effects on gene expression and enzyme activities.…”