Fig. 6: BTZ enhances the anti-HCC efficacy of AUR through induction of ChaC1. | Cell Death Discovery

Fig. 6: BTZ enhances the anti-HCC efficacy of AUR through induction of ChaC1.

From: ChaC1-based drug screenings identify a synergistic lethal effect of auranofin and proteasome inhibitors in hepatocellular carcinoma cells

Fig. 6: BTZ enhances the anti-HCC efficacy of AUR through induction of ChaC1.The alternative text for this image may have been generated using AI.

A–C Huh7 (A), Hep3B (B) and PLC/PRF/5 (C) cells were treated as indicated for 36 h. Cells were stained with 1 µg/mL propidium iodide followed by flow cytometric analysis. D Huh7 cells were treated with 50 nM BTZ and 1 µM AUR for 12, 24 or 36 h, with/without 5 µM CHX pretreatment for 1 h. The protein expression levels of ChaC1, DDIT4 and ATF4 were determined by western blotting. E Huh7 cells were pretreated with or without cell death inhibitors (10 µM zVAD, 10 µM Nec-1, 10 µM Fer-1, 10 µM CQ, 5 mM NAC or 5 µM CHX) for 1 h, and then treated with 50 nM BTZ and 1 µM AUR for 36 h. Cells were stained with 1 µg/mL propidium iodide followed by flow cytometric analysis. F, G ChaC1 knock-down (KD) and its control Huh7 cells were treated with 50 nM BTZ and 1 µM AUR for 36 h. The protein expression levels of ChaC1, DDIT4, ATF4 and Nrf2 were determined by western blotting (F). Cell death assay was performed (G). H, I ATF4-KO Huh7 cells and their control Huh7 cells were treated with 50 nM BTZ and 1 µM AUR for 36 h. The protein expression levels of ChaC1, DDIT4, ATF4 and Nrf2 were determined by western blotting (H). Cell death was measured by propidium iodide (1 µg/mL) staining and flow cytometric analysis (I). J Graphical Abstract: Overexpression of exogenous ChaC1 or induction of endogenous ChaC1 by proteasome inhibitors enhances AUR-induced HCC cell death by synergistically triggering dysregulation of thiol-disulfide homeostasis.

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