Oxidative degradation of alpha-tocopherol by reactive oxygen species, identifying products, and product anticancer activity.

α-Tocopherol (α-TQ) is a potent antioxidant with diverse applications in the food and pharmaceutical industries. It is susceptible to oxidation by various reactive oxygen species (ROS). This study first identifies the oxidation product of α-tocopherol produced by either HO or HOCl, which could be formed in foods and biological systems. Second, the kinetic and mechanistic aspects of these oxidation reactions are characterized. Finally, the anticancer activity of α-TQ and its oxidation products was revealed. The direct oxidation product is α-tocopheryl quinone (α-TQQ), which dimerizes through an ether linkage and undergoes addition reactions. LC-MS/MS identified new products, primarily including positional and diastereoisomers of α-TQQ dimers resulting from HO and HOCl addition. A kinetic study demonstrated that the oxidation reaction is first-order for both α-TQ and HO or HOCl. The mechanism is proposed based on the identified products and kinetic behavior. The postulated mechanism also aligns with the reaction's UV-Vis spectra, including the formation of the hemiketal (242 nm) and α-TQQ (261 nm) intermediates, as well as the addition products of the α-TQQ dimer (265 nm). α-TQQ dimer products of HO oxidation reaction exhibited 1.7-fold (IC50 264.72 µM) and 2.0-fold (IC50 253.72 µM) higher cytotoxicity than that of α-TQ (IC50 448.45 and 496.53 µM) against breast (MCF-7) and prostate (PC-3) cancer cells, respectively. These results indicate that natural α-TQ and its oxidation products, when administered at a suitable dose, can express protection against various types of cancer.