Tang Feng-Yao, Shih Chung-Jin, Cheng Li-Hao, Ho Hsin-Jung, Chen Hung-Jiun
Biomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung, Taiwan.
Mol Nutr Food Res. 2008 Jun;52(6):646-54. doi: 10.1002/mnfr.200700272.
The aberrant regulation of the phosphoinositide 3-kinase/Akt survival signaling pathway in cancer has prompted significant interest in suppression of this pathway to treat cancer. Previous studies identified an important role for phosphoinositide 3-kinase/Akt in colon cancer progression. Lycopene, a major component in tomato, exhibited potential anti-carcinogenic activity. Consumption of tomato has been associated with reduced risk of several types of human cancer. However, the inhibitory mechanisms of lycopene on the proliferation of human colon cancer have not been studied well yet. Thus we investigated the inhibitory effects of lycopene on the Akt signaling pathway in human colon cancer HT-29 cells. Lycopene inhibited cell proliferation in human colon cancer HT-29 cells with a IC(50) value of 10 microM. Lycopene treatment suppressed Akt activation and non-phosphorylated beta-catenin protein level in human colon cancer cells. Immunocytochemical results indicated that lycopene increased the phosphorylated form of beta-catenin proteins. These effects were also associated with reduced promoter activity and protein expression of cyclin D1. Furthermore, lycopene significantly increased nuclear cyclin-dependent kinase inhibitor p27(kip)abundance and inhibited phosphorylation of the retinoblastoma tumor suppressor protein in human colon cancer cells. In conclusion, lycopene inhibited cell proliferation of human colon cancer cells via suppression of the Akt signaling pathway and downstream targeted molecules.
癌症中磷酸肌醇3激酶/蛋白激酶B生存信号通路的异常调节引发了人们对抑制该通路以治疗癌症的浓厚兴趣。先前的研究确定了磷酸肌醇3激酶/蛋白激酶B在结肠癌进展中的重要作用。番茄红素是番茄中的主要成分，具有潜在的抗癌活性。食用番茄与降低多种人类癌症的风险有关。然而，番茄红素对人结肠癌增殖的抑制机制尚未得到充分研究。因此，我们研究了番茄红素对人结肠癌HT-29细胞中蛋白激酶B信号通路的抑制作用。番茄红素抑制人结肠癌HT-29细胞的增殖，IC(50)值为10微摩尔。番茄红素处理可抑制人结肠癌细胞中蛋白激酶B的激活和非磷酸化β-连环蛋白的蛋白水平。免疫细胞化学结果表明，番茄红素增加了β-连环蛋白的磷酸化形式。这些作用还与细胞周期蛋白D1的启动子活性降低和蛋白表达减少有关。此外，番茄红素显著增加人结肠癌细胞中核细胞周期蛋白依赖性激酶抑制剂p27(kip)的丰度，并抑制视网膜母细胞瘤肿瘤抑制蛋白的磷酸化。总之，番茄红素通过抑制蛋白激酶B信号通路及其下游靶向分子来抑制人结肠癌细胞的增殖。
