Antioxidants in dietary oils: their potential role in breast cancer prevention.

Edible oils contain variable amounts of natural antioxidants such as vitamin E. Antioxidants act not only to prevent lipid peroxidation and free-radical production, but also display potent anticancer activity. The vitamin E family of compounds is divided into two subgroups called tocopherols and tocotrienols, but only tocotrienols display potent anticancer activity at treatment doses that have little or no effect on normal cell growth or viability. Palm oil contains the highest concentrations of natural tocotrienols. Tocotrienols induced apoptosis or programmed cell death in breast cancer cells. Morphological and biochemical characteristics of apoptosis, such as nuclear and cytoplasmic condensation and DNA fragmentation, are mediated by the activation of cysteine proteases called caspases. Apoptosis is triggered by the activation of initiator caspases (caspase-8 or 9) that subsequently activate effector caspases (caspase-3, 6, and 7). Studies were conducted using the highly malignant +SA mouse mammary epithelial cell line to determine if tocotrienol-induced programmed cell death is mediated through the caspase-8 or caspase-9 pathway. Treatment with cytotoxic doses of tocotrienol resulted in a large increase in caspase-8 and caspase-3, but not caspase-9 activity. Combined treatment of tocotrienol with selective caspase-8 or caspase-3 inhibitors completely blocked tocotrieno-linduced apoptosis and activation of caspase-8 and caspase-3, respectively. These findings demonstrate that tocotrienol-induced apoptosis in highly malignant mammary epithelial cells is mediated through caspase-8 activation, and may provide essential information necessary for understanding the potential health benefits of these compounds in preventing and/or reducing the risk of breast cancer in women.