Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, Tennessee 37996, USA.
Mol Carcinog. 2012 Mar;51(3):280-9. doi: 10.1002/mc.20844. Epub 2011 Aug 31.
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 2.5 µg/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.
散发性乳腺癌主要归因于长期暴露于环境因素，通过涉及乳腺细胞从非癌前阶段到癌前和癌阶段的慢性致癌作用中累积遗传和表观遗传改变的多年、多步骤和多途径过程。流行病学和实验研究表明，绿茶成分可用作乳腺癌控制的预防剂。在我们的研究中，我们开发了一种细胞模型，模拟乳腺细胞在慢性致癌作用下由环境致癌物的低剂量累积暴露引起的癌变。在这项研究中，我们使用我们的慢性致癌模型作为靶系统，研究绿茶儿茶素提取物（GTC）在非细胞毒性水平下对累积暴露于皮摩尔 4-（甲基亚硝氨基）-1-（3-吡啶基）-1-丁酮（NNK）和苯并[a]芘（B[a]P）诱导的细胞癌变的干预作用。我们发现，GTC 在非细胞毒性、生理上可实现的 2.5 µg/mL 浓度下有效抑制 NNK 和 B[a]P 诱导的细胞癌变，如通过降低获得的与癌症相关的特性来衡量，即对生长因子的依赖性降低、非锚定依赖性生长、细胞迁移增加和腺泡形态破坏。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 途径激活、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。
