Fig. 5: PHKG2 enhances ferroptosis sensitivity via the NRF2/GPX4 pathway in vitro and in vivo. | Cell Death & Disease

Fig. 5: PHKG2 enhances ferroptosis sensitivity via the NRF2/GPX4 pathway in vitro and in vivo.

From: Transcriptional activation of PHKG2 by TP53 promotes ferroptosis through nuclear export of NRF2 in head and neck squamous cell carcinoma

Fig. 5

Western blot analysis revealed that the NRF2 activator Carnosol increased nuclear NRF2 and GPX4 protein levels following Erastin treatment, whereas PHKG2 overexpression significantly reversed these increases (A). qRT-PCR analysis demonstrated that Carnosol treatment under ferroptotic stress elevated GPX4, GSS, GCLC, and GCLM mRNA levels, which were subsequently suppressed by PHKG2 overexpression (*p < 0.05, **p < 0.01, ***p < 0.001) (B). Biochemical assays showed that PHKG2 overexpression antagonized Carnosol-induced elevation in GSH and reduction in MDA (**p < 0.01, ***p < 0.001) (C, D). Fluorescence assays for ROS and Fe2+ confirmed that PHKG2 overexpression restored ferroptotic sensitivity reduced by Carnosol treatment (E, F). In xenograft mouse models, PHKG2 knockdown impaired Erastin-induced tumor regression and decreased PP1 activation in tumors (G–I). Western blotting and ROS analysis revealed increased NRF2 and GPX4 expression and reduced ROS levels following PHKG2 knockdown (J, K).

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