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Studies on the preventive effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on 17b‐estradiol epoxidation and the potential against breast cancer carcinogenesis at the initiation
Author(s) -
Yu FuLi,
Greenlaw Roger,
Bender Wanda,
Berbeka Katarzyna
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a564-b
Subject(s) - docosahexaenoic acid , eicosapentaenoic acid , carcinogenesis , breast cancer , cancer , medicine , chemistry , cancer research , oncology , endocrinology , biochemistry , fatty acid , polyunsaturated fatty acid
We found that 17‐estradiol (E 2 ) could be activated by the versatile epoxide‐forming oxidant dimethyldioxirane (DMDO) to inhibit nuclear RNA synthesis and to bind DNA forming 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, we proposed E 2 epoxidation is the underlying mechanism for the initiation of breast cancer. A method to screen chemopreventive agents against breast cancer, at the initiation, was developed. This report is to examine the transcriptional and DNA binding properties of EPA and DHA, and the preventive effect on E 2 epoxidation. We found that both EPA and DHA were able to strongly prevent the formation of E 2 epoxide as reflected by the loss of the ability of E 2 to inhibit nuclear RNA synthesis. Additionally, we found that EPA and DHA were able to prevent the binding of [ 3 H]labeled E 2 to DNA. This preventive effect of EPA and DHA on the binding of E 2 to DNA was further confirmed when liver microsomes were used for the activation. We believe that this is the first report on the transcriptional and DNA binding properties of EPA and DHA, and their inhibitory effect on the formation of E 2 epoxide. As a dietary supplement, EPA and DHA may have the potential to prevent E 2 induced breast cancer carcinogenesis at the initiation [This work was partially supported by an Excel Academic Award from SwedishAmerican Hospital].