The combination treatment-enhanced apoptosis is mediated by TNFα, TRAF3 and GADD45α in HCC cells. Relative mRNA level of (A). TRAF3, (D). TNFα, and (G). GADD45A in HepG2 cells after the respective siRNA-mediated knockdown of the gene, negative control (NC)-siRNA served as control. Protein expression levels of cleaved-PARP, cleaved-caspase 8 and cleaved-caspase 3 in (B). TRAF3-knockdown cells (si-TRAF3-HepG2) and control cells (si-TRAF3-NC), (E). TNFα-knockdown cells (si-TNFα-HepG2) and control cells (si-TNF-NC), (H). GADD45a-knockdown cells (si-GADD45A-HepG2) and control cells (si-GADD45A-NC), after the treatment with ATN (10 μM), WOG (10 μM) or the combination of both for 48 h. Flow cytometry analysis of the percentage level of early and late apoptosis in (C). si-TRAF3-HepG2, (F). si-TNFα-HepG2 and (I). si-GADD45A-HepG2 cells after the treatment with ATN (10 μM), WOG (10 μM) or the combination of both for 48 h. Shown is mean ± SE, n = 3 independent experiments. **p < 0.01 compared to control, a<0.05, aa<0.01 compared with ATN; b < 0.05 compared with WOG. ATN, artesunate; WOG, wogonin; TRAF3, TNF receptor-associated factor 3; TNF, tumor necrosis factor; GADD45A, growth arrest and DNA-damage-inducible alpha; PI, propidium iodide; Cleaved-PARP, cleaved-poly-(ADP-ribose) polymerase.