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Notably, the ferroptosis inhibitor Ferrostatin-1 exacerbated CGAs toxicity, while the inducer Erastin attenuated it (Supplementary Figure S2C), suggesting that the profound iron deficiency we describe disrupts fundamental metabolism in a manner distinct from, and prior to, the execution of classical ferroptosisa pathway CGA has been shown to inhibit in other contexts via Nrf2/GPX4 activation (Figures 5D,E), and a concentration of 800 M CGA induced significant ROS accumulation, activating the ROS-Erk1/2 stress pathway (Figure 7

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On the Contrary, CpG islands in the promoter region of tumor suppressor genes (TSGs) are unmethylated and associated with open euchromatin conformation (12, 16)

10.3390/nano8090637 28 Garca-lvarezR.HadjidemetriouM.Snchez-IglesiasA.Liz-MarznL

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