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

Abstract

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 H<inf>2</inf>O<inf>2</inf> 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 H<inf>2</inf>O<inf>2</inf> and HOCl addition. A kinetic study demonstrated that the oxidation reaction is first-order for both α-TQ and H<inf>2</inf>O<inf>2</inf> 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 H<inf>2</inf>O<inf>2</inf> 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.