Evidence for the preventive effect of the polyunsaturated phytol side chain in tocotrienols on 17 beta-estradiol epoxidation

Background: We found that 17 beta-estradiol (E-2) could be activated by epoxidation to bind DNA and to inhibit nuclear RNA synthesis. Vitamin E compounds are powerful antioxidants and chain-breaking free radical scavengers. The chromanol ring in Vitamin E is believed to be involved in these reactions. Methods: Here, we examined the preventive effect of a-tocopherol, alpha-, gamma- and delta-tocotrienols on E-2 activation. Results: We found that when any one of these Vitamin E compounds was mixed with E-2 for epoxidation by the epoxide-forming oxidant dimethyldioxirane (DMDO), a-tocopherol was the least effective as compared with the tocotrienols against the formation of E-2 epoxide as reflected by the loss of the ability of E-2 to inhibit nuclear RNA synthesis. This conclusion was further confirmed by the binding studies of [H-3] labeled E-2 to DNA using either DMDO or liver microsomes activation system. Conclusions: Since the chromanol ring is shared by both tocopherols and tocotrienols and the only difference between these two subgroups of Vitamin E is the phytol side chain, we conclude that the polyunsaturated phytol group in tocotrienols plays a key preventive role in E-2 epoxidation. This is the first report showing that the polyunsaturated phytol side chain in tocotrienols is involved in an antioxidative activity and it may also have a preventive effect against the E-2 epoxide induced breast cancer carcinogenesis at the initiation. (c) 2005 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.