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New Drugs 32 , 465472 (2014)

Depleting intracellular GSH with buthionine sulfoximine increases elesclomol (ES)-induced human hepatocellular carcinoma JHH7 cell death, whereas the copper chelator TTM combined with elesclomol (ES) treatment of human non-small cell lung cancer ABC1 cells does not affect their growth in the presence of elesclomol (ES), indicating that elesclomol participates in promoting a unique copper-dependent cell death, which cannot be blocked by apoptosis inhibitors ( The copper-induced demise involves a protein lipoylation process, a rare and highly conserved lysine post-translational modification, which has only been observed in four lipoylated protein complexes in mammals: pyruvate dehydrogenase (PDH), alpha-ketoglutarate dehydrogenase (KDH), branched-chain alpha-keto acid dehydrogenase (BCKDH), and the glycine cleavage system (GCV) ( Figure 5