Fig. 9: JQ1 regulates ferritinophagy and the expression of ferroptosis-associated genes via epigenetic suppression of BRD4. | Cell Death & Disease

Fig. 9: JQ1 regulates ferritinophagy and the expression of ferroptosis-associated genes via epigenetic suppression of BRD4.

From: Ferritinophagy is required for the induction of ferroptosis by the bromodomain protein BRD4 inhibitor (+)-JQ1 in cancer cells

Fig. 9

a, b Enhancement of H3K4me3 (a) and H3K27ac (b) at loci upstream of BRD4 in cancer cells from ENCODE (www.encodeproject.org/). c Under treatment with JQ1 (10 μM, 24 h), the expression of the histone lysine methyltransferase G9a was suppressed and expression of the histone deacetylase SIRT1 was increased in the MDA-MB-231, Hs578T, and A549 cancer cell lines. d The expression of the ferroptosis-associated genes GPX4, SLC7A11, and SLC3A2 was downregulated under treatment with G9a inhibitor BIX-01294 (10 μM, 24 h) or SIRT1 activator CAY10602 (5 μM, 24 h). An equal volume of dimethyl sulfoxide (DMSO) was used as the control. The expression values were normalized to GAPDH expression. The expression value of the DMSO group was normalized to 1. e Expression of the autophagy markers LC3B-II/LC3B-I was increased and that of SQSTM1 and FTH1 was decreased under treatment with BIX-01294 (10 μM, 24 h) or CAY10602 (5 μM, 24 h). f–g The levels of iron (f) and reactive oxygen species (ROS) (g) were increased under treatment with BIX-01294 (10 μM) or CAY10602 (5 μM). An equal volume of DMSO was used as the control, and levels of iron and ROS were assessed after the application of the drugs for 24 h. *P < 0.05, **P < 0.01, ***P < 0.001. The data represent the results of at least three independent experiments

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