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.

• Authors: K Briviba, S L Abrahamse, B L Pool-Zobel, G Rechkemmer
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 41 Issue 1-2 Pg. 172-9 ( 2001) ISSN: 0163-5581 [Print] United States
• PMID: 12094622 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthocyanins
• Glycosides
• Quaternary Ammonium Compounds
• Sodium-Hydrogen Exchangers
• Neurotensin
• Epidermal Growth Factor
• Ammonia
• cyanidin
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases
• Calcium

Topics

• Ammonia (administration & dosage)
• Anthocyanins (pharmacology)
• Calcium (metabolism)
• Cell Division (drug effects)
• Colonic Neoplasms (metabolism)
• Diet
• Epidermal Growth Factor (pharmacology)
• Glycosides (pharmacology)
• Humans
• Hydrogen-Ion Concentration
• Kinetics
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases (metabolism)
• Neurotensin (pharmacology)
• Phosphorylation
• Quaternary Ammonium Compounds (administration & dosage)
• Sodium-Hydrogen Exchangers (metabolism)
• Tumor Cells, Cultured