Lin Jen-Kun
Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei.
Arch Pharm Res. 2002 Oct;25(5):561-71. doi: 10.1007/BF02976924.
The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, PI3K, phosphatases, ras, raf, MAPK cascades, N x FB, I x B kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The I x B kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gallate (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of I x B x and I x B x in activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkappaB activation as well as c-myc, c-jun and c-fos expression.
源自草药和可食用植物的几种化学预防剂的作用机制已成为癌症研究中引人关注的问题。茶是全球消费最为广泛的饮品。近来，对茶的癌症化学预防作用展开了深入研究。已证实茶的活性成分归因于其茶多酚。最近，在阐明茶和茶多酚进行癌症化学预防的分子机制方面取得了巨大进展。我们实验室及其他研究机构已对茶多酚对包括生长因子受体酪氨酸激酶、细胞因子受体激酶、PI3K、磷酸酶、ras、raf、MAPK级联反应、NxFB、IxB激酶、PKA、PKB、PKC、c-jun、c-fos、c-myc、cdks、细胞周期蛋白及相关转导蛋白在内的多种肿瘤生物标志物的抑制作用进行了研究。发现包括（-）表没食子儿茶素-3-没食子酸酯（EGCG）、茶黄素（TF-1）、茶黄素-3-没食子酸酯（TF-2）和茶黄素-3,3'-双没食子酸酯（TF-3）在内的多种茶多酚可抑制脂多糖激活的小鼠巨噬细胞（RAW 264.7细胞）中的IxB激酶（IKK）活性。TF-3比其他茶多酚更强烈地抑制激活的巨噬细胞中的IKK活性。TF-3抑制IKK1和IKK2活性，并阻止激活的巨噬细胞中IxBx和IxBx的降解。结果表明，TF-3和其他茶多酚对IKK活性的抑制可能是通过直接作用于IKK或信号转导途径中的上游事件实现的。TF-3和其他茶多酚可阻断胞质部分中IB的磷酸化，抑制NFB活性，并抑制激活的巨噬细胞中诱导型一氧化氮合酶水平的升高。TF-3和其他茶多酚还强烈抑制黄嘌呤氧化酶、环氧化酶、EGF受体酪氨酸激酶和蛋白激酶C的活性。这些结果表明，TF-3和其他茶多酚可能通过阻断信号转导来抑制肿瘤促进和炎症，从而发挥其癌症化学预防作用。这种抑制机制可能是由于通过调节EGFR功能、MAPK级联反应、NFκB激活以及c-myc、c-jun和c-fos表达来阻断有丝分裂和分化信号。
