Fig 2: Early commitment of p53-tg-CPCs. (a-c) GATA4 is expressed (left, white) in EGFP-positive cells (right, green) distributed within the damaged diabetic myocardium. Cardiomyocytes are labeled by troponin I (right, TnI: red).

Fig 3: FL3 sensitizes A549Res cells but not H1299 cells to cisplatin. Sub-lethal treatment with cisplatin increased Oct-3 expression in A549Res cells (p<0.05) (A). The synthetic flavagline FL3 sensitized A549Res cells to cisplatin as measured by DNA fragmentation (p<0.001) (B) and caspase 3 and 7 activation (p<0.001) (C), Treatment with 50nM of FL3 combined with cisplatin did not increase DNA fragmentation on H1299, but increased caspase 3 and 7 activation, when compared to cisplatin alone (p<0.001) (D, E, respectively). In A549 cells, Jarid1b expression is increased upon FL3 treatment (p<0.05) (F). However, P53 expression is also increased upon FL3 treatment (p<0.001) (G, H). P53 inhibition by pifithrin-µ does not protects A549Res to cisplatin-induced cell death through DNA fragmentation assay but caspase 3 and 7 activation is lowered (p<0.001) (I, J, respectively). Data represent the mean of three independent experiments. FL3 treatment was kept during all experiment for H1299 and A549Res cells.

Fig 4: Schematics illustrate the identified signaling cascade triggered by SCH treatment. In TNBC cells, SCH treatment causes DNA damage (increased phosphorylation levels of H2AX, ATM, p53, ATR, and CHK1), which leads to cell-cycle arrest. At the same time, SCH treatment suppresses DNA repair (reduced RAD51 and FANCD2), and DNA repair failure finally leads to apoptosis.

Fig 5: Mutant p53 increases ??m without damaging mtDNA. a Melanoma cell lines A375 (WTp53) and MeWo (mutant p53) were transfected with control or siRNA-p53. H2O2 production was evaluated with the Amplex Red Kit, whereas UCP2 and p53 levels were determined by RT-qPCR. *p < 0.05. b Protein expression analysis of p53 and UCP2 was performed by western blotting and normalized to GAPDH expression. *p < 0.05. c Mitochondrial membrane potential (??m) was determined by TMRM fluorescencent probe, and mtDNA damage was evaluated with a qPCR approach as described in Material and Methods section. *p < 0.05 CTRL vs siRNA-p53. The experiments are representative of three biological replicates