Fig. 8: SB-T-101141 induces cell death via the iron-dependent JNK and PERK signaling. | Cell Death & Disease

Fig. 8: SB-T-101141 induces cell death via the iron-dependent JNK and PERK signaling.

From: A novel taxane SB-T-101141 triggers a noncanonical ferroptosis to overcome Paclitaxel resistance of breast cancer via iron homeostasis-related KHSRP

Fig. 8

A The mRNA deep sequencing of MCF-7 upon SB-T-101141 (3 μM) treatment at the indicated time. Red rectangle indicates the MAPK signaling pathway. B Immunofluorescence of G3BP1-labeled granules in MCF-7 cells upon Paclitaxel or SB-T-101141 treatment for 4 h (left panel). Bar indicates 10 μm. The results were quantified (right panel) and analyzed using the student t test (mean ± SD, n = 3). *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. C–F Immunoblots of the indicated proteins in MCF-7 and MDA-MB-453 (C), MCF-7PR and MDA-MB-231PR (D) cells treated with the indicated concentrations of Paclitaxel or SB-T-101141 for 24 h (left panels) or 48 h (right panels). Immunoblots of the indicated proteins in MCF-7 and MDA-MB-453 (E), or MCF-7PR and MDA-MB-231PR (F) cells. Cells were pretreated with DFOM (D, MCF-7PR, 100 μΜ; MDA-MB-231PR, 30 μM) and/or NAC (5 mM) for 1 h, and then with indicated concentrations of Paclitaxel or SB-T-101141 (MCF-7, 3 μM; MDA-MB-453, 8 μM; MCF-7PR, 1.5 μΜ; MDA-MB-231PR, 170 nM) for 24 h (MCF-7PR) or 48 h (MDA-MB-231PR). G Immunoblots of MAPK signaling-associated proteins in the KHSRP knock-down and its counterpart MCF-7 cells treated with SB-T-101141 (3 μM) for 24 h. H, I LDH detection of MCF-7 cells (H) or MDA-MB-453 (I) cells pretreated with SP600125, SB202190 or GSK2606414 for 1 h, followed by Paclitaxel or SB-T-101141 (MCF-7, 3 μM; MDA-MB-453, 8 μM) for 24 h. All LDH release results were analyzed using the student t test (mean ± SD, n = 3). *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001.

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