Fig. 6: Imperatorin promotes TDP1 phosphorylation via the proximity-mediated effect between TDP1 and DNA-PKcs.

A, B Molecular docking of imperatorin, TDP1, and DNA-PKcs in two and three dimensions. C Representative images and quantification of the binding of TDP1 and DNA-PKcs proteins after imperatorin treatment. N = 6 repeats/group. *p < 0.05 vs. Control. D Representative images and quantification of phosphorylated TDP1 expression after imperatorin treatment and siRNA-DNA-PKcs transfection. N = 6 repeats/group. *p < 0.05 vs. Control. E DNA end-joining assays after imperatorin treatment and siRNA-DNA-PKcs transfection. Representative images and quantification of Ki67+ (F) and pH3+ (G) cardiomyocytes after imperatorin treatment and siRNA-DNA-PKcs transfection. Scale bar, 40 μm. N = 6 repeats/group, ~500 cells/repeat. *p < 0.05 vs. siRNA-scramble, #p < 0.05 vs. siRNA-scramble+Imperatorin. Representative images and quantification of γH2AX (H) and p-ATM (I) intensity after imperatorin treatment and siRNA-DNA-PKcs transfection. Scale bar, 40 μm. N = 6 repeats/group, ~50 cells/repeat. *p < 0.05 vs. siRNA-scramble, #p < 0.05 vs. siRNA-scramble+Imperatorin.