Evidence for the preventive effect of the polyunsaturated phytol side chain in tocotrienols on 17beta-estradiol epoxidation.
BACKGROUND
We found that 17beta-estradiol (E2) 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 alpha-tocopherol, alpha-, gamma- and delta-tocotrienols on E2 activation.


RESULTS
We found that when any one of these Vitamin E compounds was mixed with E2 for epoxidation by the epoxide-forming oxidant dimethyldioxirane (DMDO), alpha-tocopherol was the least effective as compared with the tocotrienols against the formation of E2 epoxide as reflected by the loss of the ability of E2 to inhibit nuclear RNA synthesis. This conclusion was further confirmed by the binding studies of [3H] labeled E2 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 E2 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 E2 epoxide induced breast cancer carcinogenesis at the initiation.
Yu
Fu-Li
FL
Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, 1601 Parkview Avenue, Rockford, IL 61107, USA. Fuliyu@uic.edu
Gapor
Abdul
A
Bender
Wanda
W
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000517:prevention & control; D004852:Epoxy Compounds / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010836:Phytol / Q000494:pharmacology*; D015138:RNA, Nuclear / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism; D024508:Tocotrienols / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D004852:Epoxy Compounds; D015138:RNA, Nuclear; D024508:Tocotrienols; D010836:Phytol; D004958:Estradiol; C064455:dimethyldioxirane