Briviba K, Abrahamse S L, Pool-Zobel B L, Rechkemmer G
Institute for Nutritional Physiology, Federal Research Center for Nutrition, D-76131 Karlsruhe, Germany.
Nutr Cancer. 2001;41(1-2):172-9. doi: 10.1080/01635581.2001.9680629.
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.
膳食多酚，包括花青素及其糖苷花色苷，被认为与水果和蔬菜对癌症的保护作用有关。关于花青素/花色苷对由神经降压素和表皮生长因子（EGF）等生长因子诱导的细胞过程的影响，目前可用的数据非常少，而这些生长因子与结肠癌的病理生理学有关。在此，我们表明，神经降压素和EGF导致人癌细胞系HT29克隆19A的细胞外酸化率增加，这可能反映细胞代谢的活性。神经降压素和EGF还导致细胞内Ca2+浓度大幅升高，诱导细胞外信号调节激酶（ERK1和ERK2）磷酸化，并刺激人癌细胞生长。矢车菊素（10微摩尔），而非其糖苷花青苷和锦葵色素-3-阿拉伯糖苷，能够抑制神经降压素和EGF诱导的细胞外酸化率增加。与Na+/H+交换抑制剂N-乙基-N-异丙基阿米洛利不同，矢车菊素不会改变由NH3/NH4+加载的细胞的细胞内pH恢复率，这表明矢车菊素抑制细胞代谢，而非直接改变Na+/H+交换。矢车菊素，而非花青苷和锦葵色素-3-阿拉伯糖苷，能够抑制神经降压素诱导的细胞内Ca2+浓度增加。在≤100微摩尔时，神经降压素和EGF诱导的ERK磷酸化不受矢车菊素、花青苷和锦葵色素-3-阿拉伯糖苷的影响。只有矢车菊素（100微摩尔），而非花青苷和锦葵色素-3-阿拉伯糖苷，能够抑制EGF诱导的细胞生长。因此，这些发现表明，膳食多酚矢车菊素，而非其糖苷，是有丝分裂原诱导的代谢活性、细胞内游离Ca2+增加和培养的结肠癌细胞生长的有效抑制剂。
