Hypoxic environment mitigates glucose deprivation-induced cell death by regulating reactive oxygen species

Abstract

Overcoming metabolic stress is a critical step for solid tumor growth. However, the underlying mechanisms of cell death and survival under metabolic stress are not well understood. In this study, we observed that hypoxia-exposed cancer cells showed increased survival under glucose deprivation accompanied by reduced SAPK/JNK signaling pathway, high NADPH/NADP ratio compared with glucose-deprived cells under normoxic condition. Since antioxidant NAC (sodium acetyl cysteine) rescued glucose deprivation-induced cell death, we measured ROS level of hypoxia-exposed cells under glucose deprivation. Glucose-deprived cells showed drastic increase of ROS production in normoxia whereas hypoxia-exposed cells showed moderate increase of ROS after glucose deprivation although basal ROS production is higher in hypoxic cells under normal glucose condition. These data indicate that hypoxic cells are resistant to glucose deprivation-induced cell death probably through regulating redox balance.