Figure 5.

ROS mediate the xCT-related glucose dependency. (A) When nutrients are sufficient, cancer cells use glucose and glutamine to produce energy and antioxidants to balance the intracellular ROS and mtROS. (B) During glucose deprivation, the production of energy and antioxidants is decreased (gray). xCT upregulation promotes the import of cystine by exchanging glutamate. AMPK is also activated to regulate the antioxidant function of SIRT3. The knockdown of SIRT3 increases the expression of xCT, increases the ROS levels, and enhances the glucose dependency of cancer cells. The antioxidant N-acetyl-cysteine (NAC) is able to prevent glucose-deprivation-induced cell death. The glutathione biosynthesis inhibitor L-buthionine-S, R-sulfoximine (BSO) enhances glucose-deprivation-induced cell death. These results revealed that ROS are involved in xCT-related glucose dependency.