Muley Pratik, Olinger Alex, Tummala Hemachand
a Department of Pharmaceutical Sciences , South Dakota State University , Brookings , South Dakota , USA.
Nutr Cancer. 2015;67(3):514-22. doi: 10.1080/01635581.2015.1002626. Epub 2015 Mar 9.
2-Deoxyglucose (2DG) is an anticancer drug with excellent safety profile. Because of its higher dose requirements, its potential is yet to translate into a monotherapy. However, recently, 2DG has been tested as an adjunct in established chemotherapeutic regimens. 2DG enhanced the potency of several chemotherapeutic agents but not all. The rationale selection of known chemotherapeutic agents to use with 2DG is hampered because of the lack of complete understanding of mechanism behind 2DG anticancer effects. Although, 2DG is a well-known glycolytic inhibitor, which inhibits the key glycolytic enzyme hexokinase, its anticancer effects cannot be fully explained by this simplistic mechanism alone. In this article, we have shown for the first time that 2DG induced a transient expression of p21 and a continuous expression of p53 in colorectal cancer cells (SW620). The treatment also caused cell cycle arrest at G0/G1 phase and induced apoptosis through the mitochondrial pathway. The effects of 2DG on p21 and p53 protein levels were totally independent of its inhibitory effect on either hexokinase or ATP levels. Results from this study provides key insights into novel molecular mechanisms of 2DG and directs rational selection of other anticancer drugs to combine with 2DG in colorectal cancer treatment.
2-脱氧葡萄糖（2DG）是一种具有出色安全性的抗癌药物。由于其所需剂量较高，其潜力尚未转化为单一疗法。然而，最近，2DG已作为既定化疗方案中的辅助药物进行了测试。2DG增强了几种化疗药物的效力，但并非全部。由于对2DG抗癌作用背后的机制缺乏全面了解，阻碍了与2DG联合使用的已知化疗药物的合理选择。尽管2DG是一种著名的糖酵解抑制剂，可抑制关键糖酵解酶己糖激酶，但其抗癌作用不能仅通过这种简单机制得到充分解释。在本文中，我们首次表明2DG在结肠癌细胞（SW620）中诱导了p21的瞬时表达和p53的持续表达。该处理还导致细胞周期停滞在G0/G1期，并通过线粒体途径诱导细胞凋亡。2DG对p21和p53蛋白水平的影响完全独立于其对己糖激酶或ATP水平的抑制作用。这项研究的结果为2DG的新分子机制提供了关键见解，并指导了在结直肠癌治疗中与2DG联合使用的其他抗癌药物的合理选择。
