Larsen Christine A, Dashwood Roderick H
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA.
Biochem Biophys Res Commun. 2009 Nov 20;389(3):527-30. doi: 10.1016/j.bbrc.2009.09.019. Epub 2009 Sep 8.
Colorectal cancer is the second leading cause of cancer-related deaths in the U.S. Met, the receptor for hepatocyte growth factor (HGF), is over-expressed in colon tumors and is associated with poor prognosis. Recently, the green tea polyphenol (-)-epigallocatechin gallate (EGCG) was reported to suppress Met activation in breast cancer cells. However, the possible confounding effect of hydrogen peroxide (H(2)O(2)), produced when EGCG is added to cell culture media, was not assessed. In the present study, the human colon cancer cell lines HCT116 and HT29 were used to examine the relationships between Met activation, EGCG treatment, and H(2)O(2) generation. At concentrations of 0.5, 1, and 5 microM, EGCG suppressed markedly the activation of Met in the presence of HGF. Concentrations of 10muM EGCG and below generated low amounts of H(2)O(2) (<1.5 microM), whereas higher H(2)O(2) concentrations (>5 microM) were required to directly increase the phosphorylation of Met. Moreover, suppression of Met activation by EGCG occurred in the presence or absence of catalase, suggesting that such effects were not an 'artifact' of H(2)O(2) generated from EGCG in cell culture media. We conclude that EGCG might be a beneficial therapeutic agent in the colon, inhibiting Met signaling and helping to attenuate tumor spread/metastasis, independent of H(2)O(2)-related mechanisms.
结直肠癌是美国癌症相关死亡的第二大主要原因。肝细胞生长因子（HGF）的受体Met在结肠肿瘤中过度表达，并与预后不良相关。最近，据报道绿茶多酚（-）-表没食子儿茶素没食子酸酯（EGCG）可抑制乳腺癌细胞中的Met激活。然而，当EGCG添加到细胞培养基中时产生的过氧化氢（H₂O₂）可能存在的混杂效应并未得到评估。在本研究中，使用人结肠癌细胞系HCT116和HT29来研究Met激活、EGCG处理和H₂O₂生成之间的关系。在0.5、1和5微摩尔浓度下，EGCG在存在HGF的情况下显著抑制Met的激活。10微摩尔及以下浓度的EGCG产生少量的H₂O₂（<1.5微摩尔），而直接增加Met磷酸化则需要更高的H₂O₂浓度（>5微摩尔）。此外，无论有无过氧化氢酶，EGCG对Met激活的抑制作用均会发生，这表明这种效应不是细胞培养基中EGCG产生的H₂O₂的“假象”。我们得出结论，EGCG可能是结肠中的一种有益治疗剂，可抑制Met信号传导并有助于减轻肿瘤扩散/转移，这与H₂O₂相关机制无关。
