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Glucose metabolism as assessed by ¹⁸FDG PET imaging provides prognostic information in patients with pancreatic cancer but the implications of manipulating glucose metabolism for therapeutic purposes are unknown. Based on previous results with other cancer cell types, we hypothesized that inhibition of glucose metabolism in pancreatic cancer cells would cause cell killing via oxidative stress resulting from disruptions in thiol metabolism. 2-Deoxy-d-glucose (2DG), a chemical inhibitor of glucose metabolism, and glucose deprivation induced cytotoxicity in human pancreatic cancer cells in a time-and dose-dependent manner as well as causing significant increases in metabolic oxidative stress as measured by increased glutathione disulfide accumulation and NADP⁺/NADPH ratios. Simultaneous administration of the thiol antioxidant N-acetylcysteine protected pancreatic cancer cells against the c-ytotoxic …