Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117593, Singapore.
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117593, Singapore.
Redox Biol. 2019 Jul;25:101154. doi: 10.1016/j.redox.2019.101154. Epub 2019 Mar 2.
Glucose starvation is one of the major forms of metabolic stress in cancer cells. Deprivation of glucose impairs glycolysis and the pentose phosphate pathway, which elicits oxidative stress due to enhanced production of reactive oxygen species (ROS) and impaired antioxidant system, leading to redox imbalance and cell death. Under glucose starvation, the 5' AMP-activated protein kinase (AMPK) plays a critical role in maintaining redox homeostasis and cell survival via multiple pathways, such as regulation of fatty acid metabolism and antioxidant response. Convergence of ROS and the glucose metabolic pathway reveals novel molecular targets for the development of effective cancer therapeutic strategies. Interestingly, AMPK, along with its upstream kinase liver kinase B1 (LKB1), has been regarded to play a tumor suppressor role. However, emerging studies have provided novel insights into the pro-tumor survival function of the LKB1-AMPK pathway. Therefore, targeting metabolic and oxidative stress in cancer cells, with manipulation of AMPK activity, is a promising strategy in developing novel cancer therapeutic agents.
葡萄糖饥饿是癌细胞中主要的代谢应激形式之一。剥夺葡萄糖会损害糖酵解和磷酸戊糖途径，由于活性氧（ROS）产生增强和抗氧化系统受损，导致氧化应激，从而导致氧化还原失衡和细胞死亡。在葡萄糖饥饿下，5' 腺苷单磷酸激活蛋白激酶（AMPK）通过多种途径，如脂肪酸代谢和抗氧化反应的调节，在维持氧化还原平衡和细胞存活方面发挥关键作用。ROS 和葡萄糖代谢途径的融合为开发有效的癌症治疗策略揭示了新的分子靶点。有趣的是，AMPK 及其上游激酶肝激酶 B1（LKB1）被认为具有肿瘤抑制作用。然而，新的研究为 LKB1-AMPK 通路的促肿瘤生存功能提供了新的见解。因此，针对癌细胞的代谢和氧化应激，通过操纵 AMPK 活性，是开发新型癌症治疗药物的有前途的策略。
