Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Prostaglandins Other Lipid Mediat. 2024 Oct;174:106854. doi: 10.1016/j.prostaglandins.2024.106854. Epub 2024 May 31.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplements have exhibited inconsistent effects on cancer risk, and their potential efficacy as cancer preventive agents has been increasingly questioned, especially in recent large randomized clinical trials. The role of host factors that govern EPA and DHA metabolism in relation to their impact on carcinogenesis remains understudied. Resolvins, the products of EPA and DHA oxidative metabolism, demonstrate intriguing antitumorigenic effects through mechanisms such as promoting macrophage phagocytosis of cell debris and inhibiting the production of proinflammatory chemokines and cytokines by tumor-associated macrophages (TAMs), which are crucial for cancer progression. However, clinical studies have not yet shown a significant increase in target tissue levels of resolvins with EPA and DHA supplementation. 15-Lipoxygenase-1 (ALOX15), a key enzyme in EPA and DHA oxidative metabolism, is often lost in various major human cancers, including precancerous and advanced colorectal cancers. Further research is needed to elucidate whether the loss of ALOX15 expression in colorectal precancerous and cancerous cells affects EPA and DHA oxidative metabolism, the formation of resolvins, and subsequently carcinogenesis. The findings from these studies could aid in the development of novel and effective chemoprevention interventions to reduce cancer risk.
二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）补充剂对癌症风险的影响不一致，其作为癌症预防剂的潜在功效受到越来越多的质疑，尤其是在最近的大型随机临床试验中。 调节 EPA 和 DHA 代谢的宿主因素在它们对致癌作用的影响方面的作用仍研究不足。 解析素是 EPA 和 DHA 氧化代谢的产物，通过促进巨噬细胞吞噬细胞碎片和抑制肿瘤相关巨噬细胞（TAMs）产生促炎趋化因子和细胞因子等机制表现出有趣的抗肿瘤作用，TAMs 对癌症进展至关重要。 然而，临床研究尚未表明 EPA 和 DHA 补充剂可显著增加目标组织中解析素的水平。15-脂氧合酶-1（ALOX15）是 EPA 和 DHA 氧化代谢的关键酶，在包括癌前和晚期结直肠癌在内的各种人类主要癌症中经常丢失。 需要进一步研究以阐明结直肠癌前和癌细胞中 ALOX15 表达的丧失是否会影响 EPA 和 DHA 的氧化代谢、解析素的形成以及随后的致癌作用。 这些研究的结果可能有助于开发新的有效的化学预防干预措施，以降低癌症风险。
