Department of Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu 641046, India.
Curr Pharm Des. 2021 Oct 5;27(31):3349-3369. doi: 10.2174/1381612826666210101153216.
Leukotrienes are one of the major eicosanoid lipid mediators produced due to an oxidative transformation of arachidonic acid. Subsequently, they get converted into various cellular signaling hormones by a series of enzymes of myeloid origin to mediate or debilitate inflammation. Interestingly, the available literature demonstrates the pivotal role of eicosanoids in neurodegenerative, obesity, diabetes, cardiovascular diseases, and cancers as well. The aberrant metabolism of arachidonic acid by the LOX pathway is a common feature of epithelial-derived malignancies and suggests the contributory role of dietary fats in carcinogenesis. The enzymes and receptors of the LOX pathway play a significant role in cell proliferation, differentiation and regulation of apoptosis through multiple signaling pathways and have been reported to be involved in various cancers, including prostate, colon, lung and pancreatic cancers. So far, leukotriene receptor antagonists and 5-LOX inhibitors have reached up to the clinical trials for treating various diseases. Keeping its various roles in cancer, the review highlights the components of the leukotriene synthesizing machinery, emerging opportunities for pharmacological intervention, and the probability of considering lipoxygenases and leukotriene receptors as good candidates for clinical chemoprevention studies.
白三烯是花生四烯酸氧化转化产生的主要类二十烷脂质介质之一。随后，它们通过一系列髓系来源的酶转化为各种细胞信号激素，从而介导或削弱炎症。有趣的是，现有文献表明类二十烷在神经退行性疾病、肥胖症、糖尿病、心血管疾病和癌症中也起着关键作用。LOX 途径中天麻酸的异常代谢是上皮来源恶性肿瘤的共同特征，提示膳食脂肪在致癌作用中的贡献作用。LOX 途径的酶和受体通过多种信号通路在细胞增殖、分化和细胞凋亡调控中发挥重要作用，并已被报道参与各种癌症，包括前列腺癌、结肠癌、肺癌和胰腺癌。到目前为止，白三烯受体拮抗剂和 5-LOX 抑制剂已达到临床试验阶段，用于治疗各种疾病。鉴于其在癌症中的多种作用，本综述强调了白三烯合成机制的组成部分、药理学干预的新机会，以及将脂氧合酶和白三烯受体视为临床化学预防研究的良好候选物的可能性。
