Green tea catechin extract in intervention of chronic breast cell carcinogenesis induced by environmental carcinogens.
Green tea catechin extract in intervention of chronic breast cell carcinogenesis induced by environmental carcinogens.
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DOI：
10.1002/mc.20844
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发表时间：
2012-03
影响因子：
4.6
通讯作者：
Wang, Hwa-Chain Robert
中科院分区：
文献类型：
--
作者：
Rathore, Kusum;Wang, Hwa-Chain Robert
散发性乳腺癌主要归因于长期暴露于环境因素，通过多年、多步骤、多路径的肿瘤发生过程，涉及乳腺细胞从非癌阶段到癌前期和癌阶段的慢性癌变过程中累积的遗传和表观遗传改变。流行病学和实验研究表明，绿茶成分可用作控制乳腺癌的预防剂。在我们的研究中，我们开发了一种细胞模型，可以模拟因累积暴露于低剂量环境致癌物而长期诱发的乳腺细胞癌变。在这项研究中，我们使用慢性致癌模型作为目标系统，研究绿茶儿茶素提取物（GTC）在非细胞毒性水平下干预皮摩尔4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮（NNK）和苯并[a]芘（B[a]P）诱导的细胞致癌作用的活性。我们发现，GTC 在无细胞毒性、生理上可达到的浓度 2.5μg/mL 下，可有效抑制 NNK 和 B[a]P 诱导的细胞癌变，测量方法是通过减少获得性癌症相关特性，如减少对生长因子的依赖、不依赖贴壁的生长、增加细胞流动性和腺泡构象破坏。我们还发现，干预致癌物诱导的活性氧 (ROS) 升高、细胞增殖增加、ERK 通路激活、DNA 损伤和基因表达变化可能是 GTC 预防活性的机制。因此，GTC 可用于与长期暴露于低剂量环境致癌物相关的乳腺细胞癌变的饮食和化学预防。
Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that green tea components may be used as preventive agents for breast cancer control. In our research, we have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. In this study, we used our chronic carcinogenesis model as a target system to investigate the activity of green tea catechin extract (GTC) at non-cytotoxic levels in intervention of cellular carcinogenesis induced by cumulative exposures to pico-molar 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P). We identified that GTC, at a non-cytotoxic, physiologically-achievable concentration of 2.5μg/mL, was effective in suppressing NNK- and B[a]P-induced cellular carcinogenesis, as measured by reduction of the acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, increased cell mobility, and acinar-conformational disruption. We also detected that intervention of carcinogen-induced elevation of reactive oxygen species (ROS), increase of cell proliferation, activation of the ERK pathway, DNA damage, and changes in gene expression may account for the mechanisms of GTC's preventive activity. Thus, GTC may be used in dietary and chemoprevention of breast cell carcinogenesis associated with long-term exposure to low doses of environmental carcinogens.
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影响因子：
8
作者：
Kasai, T;Inoue, M;Yokoyama, S
通讯作者：
Yokoyama, S
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
16
作者：
Gery, S;Komatsu, N;Koeffler, HP
通讯作者：
Koeffler, HP
影响因子：
3.9
作者：
Fuentes, Maren K.;Nigavekar, Shraddha S.;Huang, Emina H.
通讯作者：
Huang, Emina H.
影响因子：
2.8
作者：
Hecht, SS
通讯作者：
Hecht, SS