Manna Sugata, Mukherjee Sudeshna, Roy Anup, Das Sukta, Panda Chinmay Kr
Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata 700026, India.
J Nutr Biochem. 2009 May;20(5):337-49. doi: 10.1016/j.jnutbio.2008.04.001. Epub 2008 Jul 24.
The modulatory influence of tea polyphenols (epigallocatechin gallate, epicatechin gallate and theaflavin) on benzo[a]pyrene (B[a]P)-induced lung carcinogenesis in mice was analyzed using histopathological and molecular parameters. Progression of lung lesions was restricted at the hyperplastic stage by tea polyphenols. A significant reduction in cellular proliferative index and an increase in apoptotic index were noted in the restricted lung lesions. High expression of H-ras, c-myc, cyclin D1 and p53 genes was seen at the inflammatory stage (9th week) and in subsequent premalignant lesions, but down-regulation of H-ras at the hyperplastic stage (17th week). Expression of bcl-2 was high in hyperplastic lesions, whereas the expression of mdm2 and bcl-xl increased only at the moderately dysplastic stage (36th week). The tea polyphenols inhibited inflammatory response in the lung lesions on the 9th week, when decreased expression of H-ras and c-myc and increased expression of bax were noted. Prolonged treatment (>9th week) with tea polyphenols resulted in changes in the expression of some additional genes, such as reduced expression of cyclin D1 (from the 17th week), bcl-2 (from the 26th week; mild dysplasia) and p21 (on the 36th week), and high expression of p53 (from the 17th week) and p27 (on the 36th week). These observations indicate that the tea polyphenols can restrict B[a]P-induced lung carcinogenesis by differential modulation of the expression of p53 and its associated genes such as bax, bcl-2, mdm2, p21 and p27, along with H-ras, c-myc and cyclin D1, at different time points.
使用组织病理学和分子参数分析了茶多酚（表没食子儿茶素没食子酸酯、表儿茶素没食子酸酯和茶黄素）对苯并[a]芘（B[a]P）诱导的小鼠肺癌发生的调节作用。在增生阶段，茶多酚限制了肺部病变的进展。在受限的肺部病变中，细胞增殖指数显著降低，凋亡指数增加。在炎症阶段（第9周）及随后的癌前病变中，H-ras、c-myc、细胞周期蛋白D1和p53基因高表达，但在增生阶段（第17周）H-ras表达下调。bcl-2在增生性病变中高表达，而mdm2和bcl-xl的表达仅在中度发育异常阶段（第36周）增加。在第9周时，茶多酚抑制了肺部病变中的炎症反应，此时H-ras和c-myc表达降低，bax表达增加。茶多酚长期治疗（>第9周）导致一些其他基因表达发生变化，如细胞周期蛋白D1表达降低（从第17周开始）、bcl-2表达降低（从第26周开始；轻度发育异常）和p21表达降低（在第36周），以及p53表达升高（从第17周开始）和p27表达升高（在第36周）。这些观察结果表明，茶多酚可通过在不同时间点差异调节p53及其相关基因如bax、bcl-2、mdm2、p21和p27以及H-ras、c-myc和细胞周期蛋白D1的表达来限制B[a]P诱导的肺癌发生。
