Tang Feng-Yao, Cho Hsin-Ju, Pai Man-Hui, Chen Ye-Hsin
Biomedical Science Laboratory, Department of Nutrition, China Medical University, Taichung 40402, Taiwan.
J Nutr Biochem. 2009 Jun;20(6):426-34. doi: 10.1016/j.jnutbio.2008.05.001. Epub 2008 Aug 15.
Several studies indicated that people who live in the Mediterranean region have very low rates of chronic diseases such as cardiovascular disease and cancer. It is well known that Mediterranean-style diet is rich in vegetables, tomato, fruit, fish and olive oil. These important dietary components may contribute to lower risk of cancer. Lycopene, a major component in tomato, exhibited potential anticarcinogenic activity. Previous studies showed that consumption of fish containing eicosapentaenoic acid (EPA) correlated with reduced risk of cancer. However, the combined effects of lycopene and EPA on the proliferation of human colon cancer have not been studied well yet. Thus, we investigated the anticancer properties and therapeutic potential of lycopene and EPA in human colon cancer HT-29 cells. In this study, we determined the combined effects of lycopene and EPA on the proliferation of human colon cancer HT-29 cells. We demonstrated that low concentration of lycopene and EPA could synergistically inhibit the proliferation of colon cancer cells. The inhibitory mechanism was associated with suppression of phosphatidylinositol 3-kinase/Akt signaling pathway. Furthermore, treatment of lycopene and EPA also synergistically blocked the activation of downstream mTOR molecule. Immunocytochemical staining results revealed that lycopene and EPA could also up-regulate the expression of apoptotic proteins such as Bax and Fas ligand to suppress cell survival. In conclusion, our novel findings suggest that lycopene and EPA synergistically inhibited the growth of human colon cancer HT-29 cells even at low concentration. The inhibitory effects of lycopene and EPA on cell proliferation of human colon cancer HT-29 cells were, in part, associated with the down-regulation of the PI-3K/Akt/mTOR signaling pathway.
多项研究表明，生活在地中海地区的人患心血管疾病和癌症等慢性病的几率非常低。众所周知，地中海式饮食富含蔬菜、番茄、水果、鱼类和橄榄油。这些重要的饮食成分可能有助于降低患癌风险。番茄红素是番茄中的主要成分，具有潜在的抗癌活性。先前的研究表明，食用含有二十碳五烯酸（EPA）的鱼类与降低患癌风险相关。然而，番茄红素和EPA对人类结肠癌增殖的联合作用尚未得到充分研究。因此，我们研究了番茄红素和EPA在人结肠癌HT - 29细胞中的抗癌特性和治疗潜力。在本研究中，我们确定了番茄红素和EPA对人结肠癌HT - 29细胞增殖的联合作用。我们证明低浓度的番茄红素和EPA能协同抑制结肠癌细胞的增殖。其抑制机制与磷脂酰肌醇3激酶/蛋白激酶B信号通路的抑制有关。此外，番茄红素和EPA的处理还能协同阻断下游哺乳动物雷帕霉素靶蛋白分子的激活。免疫细胞化学染色结果显示，番茄红素和EPA还能上调凋亡蛋白如Bax和Fas配体的表达以抑制细胞存活。总之，我们的新发现表明，即使在低浓度下，番茄红素和EPA也能协同抑制人结肠癌HT - 29细胞的生长。番茄红素和EPA对人结肠癌HT - 29细胞增殖的抑制作用部分与PI - 3K/蛋白激酶B/哺乳动物雷帕霉素靶蛋白信号通路的下调有关。
