PALM OIL TOCOTRIENOLS AS ANTIOXIDANTS AND CHEMOPREVENTIVE AGENTS

Breast cancer leads all cancer incidence among American women, accounting for 32% of the 2005 estimated new cases in the United States. It is the second leading cause of cancer deaths, estimated at 40 000 yr(1). Estrogens, natural or synthetic, used widely in a variety of clinical conditions, from estrogen replacement therapy to cancer treatment, are themselves carcinogenic, causing uterine and breast cancers. However, the mechanism of their carcinogenic action is still not well understood. We found that both 17 beta-estradiol (E-2) and estrone (E-1) could be activated by the versatile epoxide-forming oxidant dimethyldioxirane (DMDO) to inhibit nuclear RNA synthesis and to bind DNA forming estrogen-DNA adducts both in vitro and in vivo. Since DNA adducts can cause mutation, and mutation is the molecular basis for the initiation of carcinogenesis, our findings strongly suggest the possibility that both E-2 and E-1 are the initiators for uterine and breast carcinogenesis. Based on this new insight, a method to screen chemopreventive agents against breast cancer, at the initiation, was developed. This screening test determines whether a chemical is able to prevent the formation of E-2 or E-1 epoxide as measured by both the loss of the ability of E-2 or E-1 to inhibit nuclear DNA-dependent RNA synthesis and the ability of [H-3] E-2 or El to bind DNA. This article summarizes the results of our recent studies on the preventive effects of Red Palm Oil, tocopherols and tocotrienols on the epoxidation of several carcinogens including E-2, E-1 and nflatoxin B-1 (AFB(1)). Our data suggest that tocotrienols are more potent chemopreventive agents than tocopherols against the epoxide formation of E-2, E-1 and AFB(1). As a dietary supplement, tocopherols and especially tocotrienols may have the potential to prevent breast and liver cancers.