One-Carbon Metabolism and Colorectal Cancer: Potential Mechanisms of Chemoprevention.
One-Carbon Metabolism and Colorectal Cancer: Potential Mechanisms of Chemoprevention.
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DOI：
10.1007/s40495-015-0028-8
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发表时间：
2015-06
影响因子：
--
通讯作者：
Rosenberg DW
中科院分区：
文献类型：
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作者：
Hanley MP;Rosenberg DW
多年来，由于叶酸在一碳代谢网络的中心位置，叶酸作为化学预防剂的效用一直受到评价。该网络负责产生核苷酸合成的前体以及DNA甲基化反应中使用的一碳部分，这两种机制在致癌过程中经常被破坏。虽然叶酸用于结肠直肠癌的化学预防仍然存在争议，但有证据表明叶酸摄入量对这些基本的细胞机制有显着影响。叶酸在核苷酸合成和结直肠癌（CRC）预防方面具有双重作用;在健康的结肠中，足够的叶酸状态对于核苷酸代谢稳态和DNA完整性的维持很重要，然而在结肠中，癌前病变降低的叶酸状态可能有助于消除转化细胞。此外，叶酸对于DNA甲基化反应中使用的一碳基团的产生是重要的，并且调节叶酸代谢可能有助于对抗癌发生期间的异常DNA甲基化。有趣的是，已经发现减少叶酸摄入量可以抑制炎症反应，这是最近流行的结直肠癌化学预防策略。在这篇综述中，我们更详细地讨论了叶酸摄入量影响的分子机制，以及它们如何与癌症化学预防相关。
For many years folic acid has been evaluated for its utility as a chemopreventive agent due to its position at the center of the one-carbon metabolic network. This network is responsible for generating precursors to nucleotide synthesis as well as the one-carbon moieties used in DNA methylation reactions, two mechanisms which are frequently disrupted during carcinogenesis. While the use of folic acid for the chemoprevention of colorectal cancer is still controversial, there is evidence that folic acid intake has significant influence on these fundamental cellular mechanisms. Folic acid has a dual role with regards to nucleotide synthesis and colorectal cancer (CRC) prevention; in a healthy colon, adequate folate status is important for nucleotide metabolism homeostasis and the maintenance of DNA integrity, however in a colon harboring premalignant lesions lowered folate status may help to eliminate transformed cells. In addition, folic acid is important for the generation of the one-carbon groups used in DNA methylation reactions, and modulation of folic acid metabolism may be useful in combating the aberrant DNA methylation during carcinogenesis. Interestingly, it has been revealed that decreased folic acid intake can dampen the inflammatory response, which has recently been a popular strategy for colorectal cancer chemoprevention. In this review we discuss the molecular mechanisms influenced by folic acid intake and how they might be relevant to cancer chemoprevention in greater detail.