Inhibition of both MEK1/2 and PI3K is necessary to block the actions of PAR2 activation on caspase-3 and PARP cleavage. HT-29 cells were serum-starved in the presence of either dimethyl sulfoxide (DMSO) or the inhibitors of MEK1/2 (U0126) (A–C), PI3K (LY294002) (D–F), or both (G–I) for 1 h prior to the addition of 2f-LI for one more hour. Apoptosis was stimulated by the addition of IFN-γ and TNF-α. Whole cell lysates were blotted for cleaved PARP and cleaved caspases-3. Blots are representative of n = 4. Statistical analysis was done by one-way ANOVA followed by Bonferroni's multiple comparisons test. *, p < 0.05; ***, p < 0.001; ****, p < 0.0001. n.s., not significant.