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具有癌症预防作用的植物化学物质作为异常COX-2表达所涉及的炎症信号传导中的限速因素。

Cancer preventive phytochemicals as speed breakers in inflammatory signaling involved in aberrant COX-2 expression.

作者信息

Surh Young-Joon, Kundu Joydeb Kumar

机构信息

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea.

出版信息

Curr Cancer Drug Targets. 2007 Aug;7(5):447-58. doi: 10.2174/156800907781386551.

Abstract

A causal association between inflammation and cancer has long been suspected. Multiple lines of compelling evidence from clinical, epidemiologic and laboratory studies support that inflammation plays a critical role in the promotion and progression stages of carcinogenesis. Recent progress in our understanding of the molecular biology of cancer highlights the intracellular signal transduction network, including that involved in mediating the inflammatory response, which often functions abnormally during carcinogenesis. One of the key players in inflammatory signaling is cyclooxygenase-2 (COX-2). Aberrant upregulation of COX-2 is frequently observed in various precancerous and malignant tissues. Pro-inflammatory stimuli trigger the activation of an intracellular signal transduction network comprising proline-directed serine/threonine kinases, and their downstream transcription factors, resulting in an inappropriate induction of COX-2. Therefore, the normalization of inappropriately overamplified signaling cascades implicated in chronic inflammation-associated carcinogenesis by use of COX-2 specific inhibitors has been recognized as a rational and pragmatic strategy in molecular target-based cancer prevention. This review highlights the cancer preventive effects of some anti-inflammatory phytochemicals derived from edible plants, and their underlying molecular mechanisms with a focus on representative transcription factors and upstream kinases responsible for COX-2 induction.

摘要

炎症与癌症之间的因果关联长期以来一直受到怀疑。来自临床、流行病学和实验室研究的多条令人信服的证据支持炎症在致癌作用的促进和进展阶段起着关键作用。我们对癌症分子生物学的最新认识进展突出了细胞内信号转导网络,包括参与介导炎症反应的网络,该网络在致癌过程中常常功能异常。炎症信号传导中的关键参与者之一是环氧化酶-2(COX-2)。在各种癌前和恶性组织中经常观察到COX-2的异常上调。促炎刺激触发由脯氨酸定向的丝氨酸/苏氨酸激酶及其下游转录因子组成的细胞内信号转导网络的激活,导致COX-2的不适当诱导。因此,通过使用COX-2特异性抑制剂使与慢性炎症相关致癌作用中不适当过度放大的信号级联正常化,已被认为是基于分子靶点的癌症预防中的一种合理且实用的策略。本综述重点介绍了一些源自可食用植物的抗炎植物化学物质的癌症预防作用及其潜在的分子机制,重点关注负责COX-2诱导的代表性转录因子和上游激酶。

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