A, HCT116 and SW480 cells were treated with either 25 μM honokiol or 5 Gy IR or both for 48 h and tested for caspase 3/7 activity. The honokiol and IR combination induces apoptosis in both the cells, when compared to untreated controls (*p<0.05). B, honokiol and IR combination induces caspase 3, an apoptosis mediator. Cells were treated with 25 μM honokiol and 5 Gy IR. After 48 h, the lysates were analyzed by western blotting for caspase 3 protein. The combination of honokiol with IR resulted in increased levels of cleaved caspase 3 when compared to either treatment alone. C, lysates from cells treated with the combination of honokiol and IR were analyzed by western blotting for Bax and Bcl-2 family proteins. The honokiol-IR combination induces proapoptotic protein Bax and reduces expression of anti-apoptotic protein Bcl-2 family proteins when compared with untreated cells or cells treated with honokiol or IR alone. D, lysates from cells incubated with 25 μM of honokiol and exposed to 5 Gy IR were analyzed by western blotting for cyclin D1, c-myc and p21 expression. The honokiol-IR combination inhibits cyclin D1 and c-myc expression compared to either honokiol or IR alone while increasing p21 expression.