Fig. 8

DDR are the major target of fisetin in irradiated cells. A phosphoproteomic study was performed in MDA-MB-468 cells, treated with or without fisetin (75 µM) for 24 h and irradiated with 4 Gy. Thirty minutes after irradiation cells were isolated and phosphoproteomics was performed as described in the Material & Methods section. A A total of 472 deregulated phosphosites (320 downregulated and 152 upregulated) and 47 deregulated total proteins were identified. B The gene ontology analysis indicates that phospho-proteins involved in DDR are the most frequently downregulated ones by fisetin in irradiated cells. The asterisks indicate significant deregulation (N = 3, *p < 0.05, **p < 0.01, ***p < 0.001; values extracted from g:profiler analysis). C The proposed signaling pathway targeted by fisetin to interfere with repair of IR-induced DS