Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin.
Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin.
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DOI：
10.1016/j.bbrc.2013.08.009
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发表时间：
2013-09-06
影响因子：
3.1
通讯作者：
Wang, Hwa-Chain Robert
中科院分区：
文献类型：
--
作者：
Sood, Shilpa;Choudhary, Shambhunath;Wang, Hwa-Chain Robert
超过85%的乳腺癌是散发性的，可归因于长期接触环境致癌物和共致癌物。为了确定能够诱发细胞癌前病变的共致癌物，我们研究了三氯卡班 (TCC)（一种常用于家庭和个人护理产品的抗菌剂）的活性。在这里，我们首次证明，长期暴露于生理上可达到的纳摩尔浓度的TCC会导致人类乳腺细胞从非癌性进展到癌前癌变。恶变前的致癌作用是通过日益获得的癌症相关特性来衡量的，这些特性包括对生长因子的依赖减少、贴壁独立生长和细胞增殖增加，但没有获得细胞致瘤性。长期接触 TCC 还会诱导 Erk-Nox 通路的组成性激活和细胞内活性氧 (ROS) 的增加。一次 TCC 暴露不仅在非癌性乳腺癌细胞中，而且在乳腺癌细胞中诱导 Erk-Nox 通路瞬时诱导、ROS 升高、细胞增殖增加和 DNA 损伤。使用这些组成性和短暂性诱导的变化作为终点，我们发现非细胞毒性姜黄素可有效干预 TCC 诱导的细胞癌前病变。我们的研究结果表明，在流行病学研究中应认真考虑 TCC 的共同致癌潜力，以揭示 TCC 在散发性乳腺癌发展中的重要性。使用 TCC 诱导的瞬时和组成性终点作为目标可能有助于识别非细胞毒性预防剂，例如姜黄素，可有效抑制 TCC 诱导的细胞癌前病变。
More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens and co-carcinogens. To identify co-carcinogens with abilities to induce cellular pre-malignancy, we studied the activity of triclocarban (TCC), an antimicrobial agent commonly used in household and personal care products. Here, we demonstrated, for the first time, that chronic exposure to TCC at physiologically-achievable nanomolar concentrations resulted in progressive carcinogenesis of human breast cells from non-cancerous to pre-malignant. Pre-malignant carcinogenesis was measured by increasingly-acquired cancer-associated properties of reduced dependence on growth factors, anchorage- independent growth and increased cell proliferation, without acquisition of cellular tumorigenicity. Long-term TCC exposure also induced constitutive activation of the Erk–Nox pathway and increases of reactive oxygen species (ROS) in cells. A single TCC exposure induced transient induction of the Erk–Nox pathway, ROS elevation, increased cell proliferation, and DNA damage in not only non-cancerous breast cells but also breast cancer cells. Using these constitutively- and transiently-induced changes as endpoints, we revealed that non-cytotoxic curcumin was effective in intervention of TCC-induced cellular pre-malignancy. Our results lead us to suggest that the co-carcinogenic potential of TCC should be seriously considered in epidemiological studies to reveal the significance of TCC in the development of sporadic breast cancer. Using TCC-induced transient and constitutive endpoints as targets will likely help identify non-cytotoxic preventive agents, such as curcumin, effective in suppressing TCC-induced cellular pre-malignancy.
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影响因子：
11.4
作者：
Schebb, Nils Helge;Inceoglu, Bora;Ahn, Ki Chang;Morisseau, Christophe;Gee, Shirley J.;Hammock, Bruce D.
通讯作者：
Hammock, Bruce D.
影响因子：
4.1
作者：
Coogan, Melinda A.;La Point, Thomas W.
通讯作者：
La Point, Thomas W.
影响因子：
2.8
作者：
Hecht, SS
通讯作者：
Hecht, SS
姜黄素负载的聚合物胶束抑制乳腺肿瘤生长和自发性肺转移
影响因子：
5.8
作者：
Liu, Lei;Sun, Lu;Wei, Yuquan
通讯作者：
Wei, Yuquan
影响因子：
4.8
作者：
Chen, Jiangang;Ahn, Ki Chang;Lasley, Bill L.
通讯作者：
Lasley, Bill L.