Neurotensin- and EGF-Induced Metabolic Activation of Colon Carcinoma Cells Is Diminished by Dietary Flavonoid Cyanidin but Not by Its Glycosides

Abstract

Dietary polyphenols, including anthocyanidins and their glycosides anthocyanins, are suggested to be involved in the protective effects of fruits and vegetables against cancer. Very few data are available concerning the effects of anthocyanidins/anthocyanins on cellular processes induced by growth factors such as neurotensin and epidermal growth factor (EGF), which are implicated in the pathophysiology of colon cancer. Here, we show that neurotensin and EGF caused an increase in the extracellular acidification rate, which could reflect the activity of cellular metabolism, in the human carcinoma cell line HT29 clone 19A. Neurotensin and EGF also caused a strong rise in the intracellular Ca2+ concentration, induced phosphorylation of extracellular signal-regulated kinases (ERK1 and ERK2), and stimulated growth of human carcinoma cells. Cyanidin (10 microM), but not its glycosides cyanin and idaein, was able to inhibit the neurotensin- and EGF-induced increased rate of extracellular acidification. In contrast to N-ethyl-N-isopropyl amiloride, an inhibitor of Na+/H+ exchange, cyanidin did not alter the rate of intracellular pH recovery of cells loaded by NH3/NH4+, indicating that cyanidin inhibits cellular metabolism, rather than directly altering Na+/H+ exchange. Cyanidin, but not cyanin and idaein, was able to inhibit an increase in intracellular Ca2+ concentration induced by neurotensin. Neurotensin- and EGF-induced phosphorylation of ERKs was not affected by cyanidin, cyanin, and idaein at < or = 100 microM. Only cyanidin (100 microM), but not cyanin and idaein, was able to inhibit cellular growth induced by EGF. Thus these findings suggest that a dietary polyphenol cyanidin, but not its glycosides, is a potent inhibitor of mitogen-induced metabolic activity, increase in free intracellular Ca2+, and cellular growth of cultured colon carcinoma cells.

Gene expression microarray analysis of the effects of grape anthocyanins in mice: a test of a hypothesis-generating paradigm

“…Previous work has focused on antioxidant and anti-inflammatory properties in relation to cardiovascular disease and maintenance of brain function with ageing 8–13. There is also evidence that anthocyanins may have anti-carcinogenic, anti-obesity and anti-diabetic effects as well 14;15;16. The availability of prior data regarding the potential health effects of anthocyanins provides an opportunity to validate our approach through corroboration of hypotheses generated from our analyses with existing published hypotheses.…”

Effects of Simulated Human Gastrointestinal Digestion of Two Purple-Fleshed Potato Cultivars on Anthocyanin Composition and Cytotoxicity in Colonic Cancer and Non-Tumorigenic Cells

“…Such findings might be related to differences in anthocyanin profiles in the FW digests, particularly the approximately two-fold greater content of the aglycone cyanidin and petunidin anthocyanins in the Leona versus Amachi colonic reactors. Cyanidin, but not its glycosides, was shown to be a potent inhibitor of the growth of human colon carcinoma HT-29 cells [ 55 ] or HCT-116 [ 56 ] and Caco-2 [ 57 ] colon cancer cells. Aglycones such as cyanidin can readily be released following intestinal microbial beta-glucosidase-mediated hydrolysis of anthocyanins [ 58 ].…”

Effect of the Atmospheric Pressure Cold Plasma Treatment on Tempranillo Red Wine Quality in Batch and Flow Systems

“…Phenolic compounds are responsible for the organoleptic characteristics of wine, such as color and flavor. Moreover, some of these compounds have been related to antioxidant and free radical-scavenging properties [3,11] that may play a role in human health, including a highly probable protection against cardiovascular diseases and cancer [12][13][14].…”