γ-tocotrienol was more potent than γ-tocopherol. γ-tocotrienol induced mammary tumor cell apoptosis with caspases activation, PARP cleavage, JNK activation, and upregulation of DR5 and CHOP levels. γ-tocotrienol increased the intracellular ceramide and dihydroceramide levels. De novo ceramide synthesis inhibitor protected the cells from tocotrienol-mediated apoptosis, JNK activation, DR5 and CHOP upregulation, and caspases activation. Here, MAPK8 is linked to breast cancer.