Vitamin E succinate and cancer treatment: a vitamin E prototype for selective antitumour activity

Great hope has been given to micronutrients as anticancer agents, since they present natural compounds with beneficial effects for normal cells and tissues. One of these is vitamin E (VE), an antioxidant and an essential component of biological membranes and circulating lipoproteins. In spite of a number of epidemiological and intervention studies, little or no correlation between VE intake and incidence of cancer has been found. Recent reports have identified a redox-silent analogue of VE, alpha-tocopheryl succinate (alpha-TOS), as a potent anticancer agent with a unique structure and pharmacokinetics in vivo. alpha-TOS is highly selective for malignant cells, inducing them into apoptotic death largely via the mitochondrial route. The molecule of alpha-TOS may be modified so that analogues with higher activity are generated. Finally, alpha-TOS and similar agents are metabolised to VE, thereby yielding a compound with a secondary beneficial activity. Thus, alpha-TOS epitomises a group of novel compounds that hold substantial promise as future anticancer drugs. The reasons for this optimistic notion are discussed in the following paragraphs.