Shikonin-induced apoptosis was caused by the activation of the AKT-caused Apoptosis Signal-Regulating Kinase 1—p38 Mitogen-Activated Protein Kinase (AKT/ASK1/p38-MAPK) pathway and the downregulation of a cyclin-dependent kinase inhibitor (p21) in several cancer cells. Here, MAP3K5 is linked to cancer.