HaCaT and NHEK cells were either unirradiated or irradiated with 500 J/m2 of UVB in the absence (“o”, 1:2000 DMSO) or presence (“+”) of 1 μM sorafenib and isolated for FACS analysis and protein extracts 24 hours later. A, HaCaT, B, NHEK cells show 45% and 80% suppression, respectively, of apoptosis in the presence of sorafenib as measured by FACS for Annexin V+, TMRE-low cells (n=6 for each condition, “***”, p<0.001). Western blots of HaCaT (C) and NHEK (D) cells probed for the MAP kinases JNK and ERK demonstrated strong phospho-JNK induction following irradiation and significant suppression by sorafenib. Phospho-ERK was slightly suppressed following irradiation, and at all time points, paradoxical hyperactivation in the presence of sorafenib was observed, particularly in HaCaT cells. Importantly, phospho-MKK4 and phospho-MKK7, upstream kinases that activate JNK, were both strongly induced by UV radiation and strongly suppressed by sorafenib.