scholarly journals NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Hyemi Lee ◽  
Eun-Taex Oh ◽  
Bo-Hwa Choi ◽  
Moon-Taek Park ◽  
Ja-Kyeong Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Cancer Cell Death

scholarly journals A synthetic lethal drug combination mimics glucose deprivation–induced cancer cell death in the presence of glucose

2020 ◽  
Vol 295 (5) ◽  
pp. 1350-1365
Author(s):  
James H. Joly ◽  
Alireza Delfarah ◽  
Philip S. Phung ◽  
Sydney Parrish ◽  
Nicholas A. Graham
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Drug Combination ◽  
Glucose Deprivation ◽  
Synthetic Lethal ◽  
Cancer Cell Death

scholarly journals Salubrinal Enhances Cancer Cell Death during Glucose Deprivation through the Upregulation of xCT and Mitochondrial Oxidative Stress

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1101
Author(s):  
Mei-Chun Chen ◽  
Li-Lin Hsu ◽  
Sheng-Fan Wang ◽  
Yi-Ling Pan ◽  
Jeng-Fan Lo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Redox Homeostasis ◽  
Glucose Deprivation ◽  
Metabolic Flexibility ◽  
Mitochondrial Oxidative Stress ◽  
Cancer Cell Death ◽  
Adaptation Response

Cancer cells have the metabolic flexibility to adapt to heterogeneous tumor microenvironments. The integrated stress response (ISR) regulates the cellular adaptation response during nutrient stress. However, the issue of how the ISR regulates metabolic flexibility is still poorly understood. In this study, we activated the ISR using salubrinal in cancer cells and found that salubrinal repressed cell growth, colony formation, and migration but did not induce cell death in a glucose-containing condition. Under a glucose-deprivation condition, salubrinal induced cell death and increased the levels of mitochondrial reactive oxygen species (ROS). We found that these effects of salubrinal and glucose deprivation were associated with the upregulation of xCT (SLC7A11), which functions as an antiporter of cystine and glutamate and maintains the level of glutathione to maintain redox homeostasis. The upregulation of xCT did not protect cells from oxidative stress-mediated cell death but promoted it during glucose deprivation. In addition, the supplementation of ROS scavenger N-acetylcysteine and the maintenance of intracellular levels of amino acids via sulfasalazine (xCT inhibitor) or dimethyl-α-ketoglutarate decreased the levels of mitochondrial ROS and protected cells from death. Our results suggested that salubrinal enhances cancer cell death during glucose deprivation through the upregulation of xCT and mitochondrial oxidative stress.

scholarly journals A synthetic lethal drug combination mimics glucose deprivation–induced cancer cell death in the presence of glucose

2019 ◽  
Vol 295 (5) ◽  
pp. 1350-1365 ◽  
Author(s):  
James H. Joly ◽  
Alireza Delfarah ◽  
Philip S. Phung ◽  
Sydney Parrish ◽  
Nicholas A. Graham
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Drug Combination ◽  
Glucose Transporter ◽  
Glucose Deprivation ◽  
Metabolic Reprogramming ◽  
Synthetic Lethal ◽  
Cancer Cell Death

Metabolic reprogramming in cancer cells can increase their dependence on metabolic substrates such as glucose. As such, the vulnerability of cancer cells to glucose deprivation creates an attractive opportunity for therapeutic intervention. Because it is not possible to starve tumors of glucose in vivo, here we sought to identify the mechanisms in glucose deprivation–induced cancer cell death and then designed inhibitor combinations to mimic glucose deprivation–induced cell death. Using metabolomic profiling, we found that cells undergoing glucose deprivation–induced cell death exhibited dramatic accumulation of intracellular l-cysteine and its oxidized dimer, l-cystine, and depletion of the antioxidant GSH. Building on this observation, we show that glucose deprivation–induced cell death is driven not by the lack of glucose, but rather by l-cystine import. Following glucose deprivation, the import of l-cystine and its subsequent reduction to l-cysteine depleted both NADPH and GSH pools, thereby allowing toxic accumulation of reactive oxygen species. Consistent with this model, we found that the glutamate/cystine antiporter (xCT) is required for increased sensitivity to glucose deprivation. We searched for glycolytic enzymes whose expression is essential for the survival of cancer cells with high xCT expression and identified glucose transporter type 1 (GLUT1). Testing a drug combination that co-targeted GLUT1 and GSH synthesis, we found that this combination induces synthetic lethal cell death in high xCT-expressing cell lines susceptible to glucose deprivation. These results indicate that co-targeting GLUT1 and GSH synthesis may offer a potential therapeutic approach for targeting tumors dependent on glucose for survival.

New Insight into 2-Methoxyestradiol- a Possible Physiological Link between Neurodegeneration and Cancer Cell Death

2016 ◽  
Vol 23 (15) ◽  
pp. 1513-1527 ◽  
Author(s):  
Magdalena Gorska ◽  
Alicja Kuban-Jankowska ◽  
Jaroslaw Slawek ◽  
Michal Wozniak
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Cancer Cell Death ◽  
Insight Into

Zinc chelator TPEN induces pancreatic cancer cell death through causing oxidative stress and inhibiting cell autophagy

2019 ◽  
Vol 234 (11) ◽  
pp. 20648-20661 ◽  
Author(s):  
Zhen Yu ◽  
Ze Yu ◽  
ZhenBao Chen ◽  
Lin Yang ◽  
MingJun Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pancreatic Cancer ◽  
Cell Death ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Death ◽  
Zinc Chelator
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