Inhibitory Effects of Different Forms of Tocopherols, Tocopherol Phosphates, and Tocopherol Quinones on Growth of Colon Cancer Cells

Tocopherols are the major source of dietary vitamin E. In this study, the growth inhibitory effects of different forms of tocopherols (T), tocopheryl phosphates (TP), and tocopherol quinones (TQ) on human colon cancer HCT116 and HT29 cells were investigated. (delta-T was more active than gamma-T in inhibiting colon cancer cell growth, decreasing cancer cell colony formation, and inducing apoptosis; however, alpha-T was rather ineffective. Similarly, the rate of cellular uptake also followed the ranking order delta-T > gamma-T >> alpha-T. TP and TQ generally had higher inhibitory activities than their parent compounds. Interestingly, the gamma forms of TP and TQwere more active than the (5 forms in inhibiting cancer cell growth, whereas the a forms were the least effective. The potencies of gamma-TQand delta-TQ (showing IC50 values of similar to 0.8 and similar to 2 mu M on HCT116 cells after a 72 h incubation, respectively) were greater than 100-fold and greater than 20-fold higher, respectively, than those of their parent tocopherols. Induction of cancer cell apopfosis by S-T, gamma-TP, and gamma-TQ was characterized by the cleavage of caspase 3 and PARP1 and DNA fragmentation. These studies demonstrated the higher growth inhibitory activity of delta-T than gamma-T, the even higher activities of the gamma forms of TP and TQ, and the ineffectiveness of the alpha forms of tocopherol and their metabolites against colon cancer cells.