Rare sugar L-sorbose exerts antitumor activity by impairing glucose metabolism.
Rare sugar L-sorbose exerts antitumor activity by impairing glucose metabolism.
复制标题
DOI：
10.1038/s42003-023-04638-z
复制
发表时间：
2023-03-11
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
稀有糖是天然丰度低的单糖。它们是膳食糖的结构异构体，但几乎不被代谢。在这里，我们报告说，罕见的糖l-山梨糖诱导各种癌细胞凋亡。作为d-果糖的C-3差向异构体，l-山梨糖通过转运蛋白GLUT 5内化并被己酮糖激酶（KHK）磷酸化以产生l-山梨糖-1-磷酸（S-1-P）。细胞S-1-P使糖酵解酶己糖激酶失活，导致糖酵解减弱。因此，线粒体功能受损并产生活性氧。此外，l-山梨糖下调KHK-A（KHK的剪接变体）的转录。由于KHK-A是抗氧化基因的阳性诱导物，因此癌细胞中的抗氧化防御机制可以通过l-山梨糖处理而减弱。因此，l-山梨糖执行多种抗癌活性以诱导细胞凋亡。在小鼠异种移植模型中，l-山梨糖与其他抗癌药物联合使用可增强肿瘤化疗的效果。这些结果表明，l-山梨糖作为一种有吸引力的治疗试剂用于癌症治疗。罕见的糖L-山梨糖显示出降低细胞活力并增加培养物中的凋亡细胞，并增强肿瘤化疗与索拉非尼联合在小鼠异种移植模型中的作用。
Rare sugars are monosaccharides with low natural abundance. They are structural isomers of dietary sugars, but hardly be metabolized. Here, we report that rare sugar l-sorbose induces apoptosis in various cancer cells. As a C-3 epimer of d-fructose, l-sorbose is internalized via the transporter GLUT5 and phosphorylated by ketohexokinase (KHK) to produce l-sorbose-1-phosphate (S-1-P). Cellular S-1-P inactivates the glycolytic enzyme hexokinase resulting in attenuated glycolysis. Consequently, mitochondrial function is impaired and reactive oxygen species are produced. Moreover, l-sorbose downregulates the transcription of KHK-A, a splicing variant of KHK. Since KHK-A is a positive inducer of antioxidation genes, the antioxidant defense mechanism in cancer cells can be attenuated by l-sorbose-treatment. Thus, l-sorbose performs multiple anticancer activities to induce cell apoptosis. In mouse xenograft models, l-sorbose enhances the effect of tumor chemotherapy in combination with other anticancer drugs. These results demonstrate l-sorbose as an attractive therapeutic reagent for cancer treatment. The rare sugar L-sorbose is shown to decrease cell viability and increase apoptotic cells in culture and to enhance the effect of tumor chemotherapy in combination with sorafenib in mouse xenograft models.
登录
查看更多内容
影响因子：
13.8
作者：
Liberti MV;Locasale JW
通讯作者：
Locasale JW
影响因子：
9.3
作者：
Abdel-Wahab, Ali F.;Mahmoud, Waheed;Al-Harizy, Randa M.
通讯作者：
Al-Harizy, Randa M.
索拉非尼对亚太地区晚期肝细胞癌患者的疗效和安全性：一项 III 期随机、双盲、安慰剂对照试验
影响因子：
51.1
作者：
Cheng, Ann-Lii;Kang, Yoon-Koo;Guan, Zhongzhen
通讯作者：
Guan, Zhongzhen
影响因子：
29
作者：
Jeong S;Savino AM;Chirayil R;Barin E;Cheng Y;Park SM;Schurer A;Mullarky E;Cantley LC;Kharas MG;Keshari KR
通讯作者：
Keshari KR
影响因子：
7.7
作者：
Asipu, A;Hayward, BE;Bonthron, DT
通讯作者：
Bonthron, DT