Fig. 3: Synergy between olaparib and ATL results from PARP-trapping.

a Both hydrogen peroxide and auranofin sensitize cancer cells to olaparib. PC-3 cells were treated by 1, 2, 4, 8, or 16 μM olaparib alone or combined with 100 μM H₂O₂ or 0.5 μM auranofin for 72 h. Olaparib in combination with 100 μM H₂O₂ or 0.5 μM auranofin dose-dependently inhibited the growth of PC-3 cells, while olaparib alone had no impact. NAC blocked H₂O₂ or auranofin-induced olaparib sensitization. b CI values between auranofin and olaparib indicate strong synergy. PC-3 or A549 cells were treated by 0.5 μM auranofin and the indicated concentrations of olaparib for 72 h. c Western blot verification of shRNA-mediated knockdown of OGG1 and PARP1 in PC-3 cells. d MTT proliferation assay. Wild-type, OGG1-depleted or inhibited by 8 μM O8, and PARP1-depleted PC-3 cells were treated by 2, 4, 8, or 16 μM olaparib in combination with 10 μM ATL for 72 h. e MTT assay. Wild-type or PARP1 depleted PC-3 cells were treated by 10 μM ATL or the combination of 10 μM ATL and 10 μM olaparib (Ola) for 72 h. PARP1 knockdown did not sensitize PC-3 cells to 10 μM ATL. f Detection of chromatin-bound PARP1 by Western blot. PC-3 cells were treated by 10 μM ATL, 10 μM olaparib (Ola), 10 μM veliparib (Vel), or the combination of 10 μM ATL with 10 μM olaparib or veliparib for 24 h. n.s. not significant, ***p < 0.001 vs. vehicle control.