Mechanisms of oxysterol-induced carcinogenesis.
Mechanisms of oxysterol-induced carcinogenesis.
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DOI：
10.1186/1476-511x-10-44
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发表时间：
2011-03-09
影响因子：
4.5
通讯作者：
Kuver R
中科院分区：
文献类型：
--
作者：
Jusakul A;Yongvanit P;Loilome W;Namwat N;Kuver R
氧固醇是胆固醇的氧化产物，其通过由细胞色素P450家族酶介导的酶促反应或通过涉及活性氧和氮物质的非酶促反应产生。氧固醇通过作为胆固醇代谢的中间体在正常细胞过程中发挥各种调节作用，例如胆固醇稳态。也已经描述了氧固醇的病理作用，并且各种报告已经暗示氧固醇在几种疾病状态中，包括动脉粥样硬化、神经疾病和癌症。许多研究表明，氧化固醇与各种类型的癌症有关，包括结肠癌、肺癌、皮肤癌、乳腺癌和胆管癌。氧固醇促进癌症发生和发展的分子机制是一个积极研究的领域。本文综述了氧化固醇在致癌作用中的作用。氧化固醇的致突变性在核和线粒体DNA中都有描述。某些氧化固醇如胆固醇-环氧化物和胆甾烷三醇已被证明具有致突变性和遗传毒性。氧固醇具有促氧化和促炎特性，可促进致癌作用。氧化固醇可诱导炎性细胞因子如白细胞介素-8和白细胞介素-1 β的产生。某些氧固醇也参与环加氧酶-2表达的诱导。炎症作用也可以通过肝-X-受体（氧固醇的核受体）的活化来介导。因此，已经描述了几种不同的分子机制，表明氧固醇有助于各种器官系统中产生的癌症的起始和进展。
Oxysterols are oxidation products of cholesterol that are generated by enzymatic reactions mediated by cytochrome P450 family enzymes or by non-enzymatic reactions involving reactive oxygen and nitrogen species. Oxysterols play various regulatory roles in normal cellular processes such as cholesterol homeostasis by acting as intermediates in cholesterol catabolism. Pathological effects of oxysterols have also been described, and various reports have implicated oxysterols in several disease states, including atherosclerosis, neurological disease, and cancer. Numerous studies show that oxysterols are associated with various types of cancer, including cancers of the colon, lung, skin, breast and bile ducts. The molecular mechanisms whereby oxysterols contribute to the initiation and progression of cancer are an area of active investigation. This review focuses on the current state of knowledge regarding the role of oxysterols in carcinogenesis. Mutagenicity of oxysterols has been described in both nuclear and mitochondrial DNA. Certain oxysterols such as cholesterol-epoxide and cholestanetriol have been shown to be mutagenic and genotoxic. Oxysterols possess pro-oxidative and pro-inflammatory properties that can contribute to carcinogenesis. Oxysterols can induce the production of inflammatory cytokines such as interleukin-8 and interleukin-1β. Certain oxysterols are also involved in the induction of cyclo-oxygenase-2 expression. Inflammatory effects can also be mediated through the activation of liver-X-receptor, a nuclear receptor for oxysterols. Thus, several distinct molecular mechanisms have been described showing that oxysterols contribute to the initiation and progression of cancers arising in various organ systems.