二十烷类化合物在癌变中的作用

4open Pub Date : 2019-01-01 DOI:10.1051/FOPEN/2018008
B. Brücher, I. Jamall
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引用次数: 9

摘要

炎症是人体对病原(生物或化学)刺激的反应,涵盖了一系列迅速发展的化合物和途径,这些化合物和途径共同作用,维持机体的健康。花生四烯酸和其他多烯脂肪酸可以通过环加氧酶和脂加氧酶途径形成类二十烷酸和相关的脂肪酸衍生物,产生多种促炎和抗炎介质,如前列腺素、白三烯、脂毒素、溶解蛋白等。细胞色素P450途径导致羟基脂肪酸的形成,如20-羟基二十碳四烯酸和环氧类二十碳烷酸。由活性氧和/或氮自由基诱导的自由基反应导致氧合脂质,如异前列腺素或异黑素,它们也表现出促炎活性。二十烷酸及其代谢产物在各种疾病的生理和病理信号传导中起着基本的内分泌、自分泌和旁分泌作用。这些分子诱导各种不饱和脂肪酸依赖的信号通路,影响串扰,改变细胞-细胞相互作用,并导致包括组织微环境在内的广泛的细胞功能障碍。虽然二十烷类化合物的完整作用,包括最近阐明的抗炎专门的促溶解脂质介质(SPMs),如脂毒素,溶解蛋白,保护蛋白和蛋白,尚不完全清楚,但持续慢性炎症的结果正在促进早期癌变。慢性炎症促进了正常细胞向癌变细胞的转变。在广泛但可识别的多种分子途径中,对体内平衡的破坏创造了一种微环境,它构成了绝大多数癌症(称为“散发性癌症”)的6步癌变序列中早期和必要的一步。
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Eicosanoids in carcinogenesis
Inflammation is the body's reaction to pathogenic (biological or chemical) stimuli and covers a burgeoning list of compounds and pathways that act in concert to maintain the health of the organism. Eicosanoids and related fatty acid derivatives can be formed from arachidonic acid and other polyenoic fatty acids via the cyclooxygenase and lipoxygenase pathways generating a variety of pro- and anti-inflammatory mediators, such as prostaglandins, leukotrienes, lipoxins, resolvins and others. The cytochrome P450 pathway leads to the formation of hydroxy fatty acids, such as 20-hydroxyeicosatetraenoic acid, and epoxy eicosanoids. Free radical reactions induced by reactive oxygen and/or nitrogen free radical species lead to oxygenated lipids such as isoprostanes or isolevuglandins which also exhibit pro-inflammatory activities. Eicosanoids and their metabolites play fundamental endocrine, autocrine and paracrine roles in both physiological and pathological signaling in various diseases. These molecules induce various unsaturated fatty acid dependent signaling pathways that influence crosstalk, alter cell–cell interactions, and result in a wide spectrum of cellular dysfunctions including those of the tissue microenvironment. Although the complete role of eicosanoids, including that of the recently elucidated anti-inflammatory specialized pro-resolving lipid mediators (SPMs), e.g. lipoxins, resolvins, protectins and maresins, is not completely understood, the result of unremitting chronic inflammation is fostering early stages of carcinogenesis. Chronic inflammation facilitates the transition from a normal cell to a cancerous one. The disruption of homeostasis across a wide, but identifiable, swath of diverse molecular pathways creates a micromilieu which constitutes an early and necessary step in the 6-step sequence of carcinogenesis for the vast majority of cancers, termed “sporadic cancers”.
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