GSH metabolism is Epoxomicin regulated by the Nrf2/antioxidant response pathway signaling pathway. Nrf2 is a transcription factor that LDK378 induces genes which promoter contains ARE, including antioxidant enzymes and phase-2 proteins of the detoxification system. Nrf2 activation has been implicated in tumor cell multidrug resistance. However, at low dose, CUR inhibited GST activity because of direct inhibition of the enzyme, not Nrf2 activity. Our data are consistent with CUR dose-dependent activation of the Nrf2 pathway since they show activation of GCL at low dose then activation of GST at high dose resulting in biphasic behavior of GSx. Another recently reported enzymatic target of CUR is glyoxylase-1, which links glycolysis to GSH metabolism through the non enzymatic and permanent formation of methylglyoxal, a side product of glycolysis. Methylglyoxal is a toxic 2-oxoaldehyde implicated in ROS production and induction of apoptosis. The simultaneous decrease of Lac and GSx levels at 50 mM curcumin in this study may be partly related to inhibition of GLO1, whereas, at low dose CUR, GLO1 activity should be unaffected. Inhibitors of GLO1 have been proposed as potential anti-carcinogenic agents. Besides GSH metabolism, another major response involved lipid and phospholipid metabolism. At low dose CUR, there were transient changes in PE and PC, two phospholipid derivatives of ethanolamine and Cho metabolism, respectively. At high dose, there was dramatic increase of tFA and PUF, to which could be related increase of Ace, and decrease of GPC and GPE, two byproducts of phospholipid metabolism originating from activity of phospholipase A2. PLA2 products are bioactive and can initiate signalling cascades that modulate cellular viability and inflammation. Lysophosphatidylcholine is further catabolized in GPC. Increased fatty acid NMR signals have been shown during accumulation of mobile lipids and onset of apoptosis. Mobile lipid accumulation was reported in cytotoxic insults with inhibitors of mitochondrial respiration involving mitochondrial damage, autophagic vacuoles and lysosomal lipid catabolism. The formation of lipid droplets is another mechanism by which tFA and PUF levels could increase. Lipid droplets are formed when cells can no longer oxidize fatty acids because of deficient mitochondrial functions. This mechanism is considered to prevent lipotoxicity and induction of apoptosis due to accumulating free fatty acids from either exogenous or endogenous sources. Taken together, free fatty acid accumulation correlates with mitochondrial damage. 
In our study, decrease of GPC and GPE was in favor of downregulation of PLA2 activity, possibly as a means for the cell to limit release in the cytosol of membrane-originating fatty acids and propagation of oxidative stress. Cyclooxygenase-2 can be induced by mitogenic and inflammatory stimuli, a mechanism which results in enhanced synthesis of prostaglandins in inflamed and neoplastic tissues. In our study, the accumulation of PUF and tFA at high dose CUR is consistent with inhibition of COX-2. Curcumin was shown to downregulate expression and activity of COX-2 and PLA2 both in vitro and in vivo. It may be proposed that increased levels of PUF and tFA and decreased levels of GPC and GPE indicate inhibition of COX-2 and PLA2, both with anti-inflammatory effect.