The overexpression of ErbB-2 receptor relates to malignant transformation of breast cancer. The present study was carried out to establish the usefulness of alpha-tocopheryloxybutyric acid (TE) as a chemotherapeutic agent for human breast cancer. TE caused induction of apoptosis in MDA-MB-453 cells overexpressing the ErbB-2 receptor. TE reduced levels of activated ErbB-2 receptor and Akt. In contrast, TE induced the activation of p38, and SB203580, a specific inhibitor for p38, attenuated the TE-induced apoptosis. These data indicate that simultaneous occurrences of Akt inhibition and p38 activation by TE result in the cell death.