Vitamin E and Breast Cancer

Vitamin E is a term that describes a group of compounds with similar yet unique chemical structures and biological activities. One interesting property possessed by certain vitamin E compounds—namely, δ-tocotrienol, RRR-α-tocopheryl succinate [vitamin E succinate (VES), a hydrolyzable ester-linked succinic acid analogue of RRR-α-tocopherol], and a novel vitamin E analogue referred to as α-TEA (α-tocopherol ether linked acetic acid analogue, which is a stable nonhydrolyzable analogue of RRR-α-tocopherol)—is their ability to induce cancer cells but not normal cells to undergo a form of cell death called apoptosis. In contrast, the parent compound, RRR-α-tocopherol, also referred to as natural or authentic vitamin E and known for its antioxidant properties, does not induce cancer-cell apoptosis. Efforts to understand how select vitamin E forms can induce cancer cells to undergo apoptosis have identified several nonantioxidant biological functions, including restoration of pro-death transforming growth factor-β and Fas signaling pathways. Recent studies with α-TEA show it to be a potent inducer of apoptosis in a wide variety of epithelial cancer cell types, including breast, prostate, lung, colon, ovarian, cervical, and endometrial in cell culture, and to be effective in significantly reducing tumor burden and metastasis in a syngeneic mouse mammary tumor model, as well as xenografts of human breast cancer cells. Studies also show that α-TEA, in combination with the cyclooxygenase-2 inhibitor celecoxib and the chemotherapeutic drug 9-nitro-camptothecin decreases breast cancer animal model tumor burden and inhibits metastasis significantly better than do single-agent treatments.