Effect of fatty acids on estradiol and testosterone binding to whole DU-145 prostate cells.
Cancer of the prostate is one of the leading causes of cancer related deaths in men. An important role in the development of prostate cancer is played by androgens and androgen ablation is therefore currently used in cancer treatment. In the past, estrogens were widely used in treatment of prostate cancer, but there are indications that estrogens could also be involved in carcinogenesis. Lately, much research has been done on the modulation of the binding of steroid hormones to their receptors by polyunsaturated fatty acids (PUFAs), which could interfere with the steroid hormone's message. Therefore, the aim of this study was to determine in whole DU-145 human prostate cells the effect of EFAs and their metabolites on the binding and affinity of the estrogen receptor (ER) and androgen receptor (AR) to estradiol (E(2)) and testosterone (T), respectively. Fatty acids were dissolved in ethanol and added to the cell culture in a final ethanol concentration of 0.2% on the fourth day of incubation. The results showed that the PUFAs under investigation inhibited the AR's capacity, in contrast to the ER's capacity which was stimulated. However, the dissociation constants (K(d)) of the AR and ER complexes in the presence of the PUFAs, were as follows. Except for eicosapentaenoic acid (EPA) which decreased the AR dissociation constant and EPA and alpha-linolenic acid (ALA) which increased the ER dissociation constant, the remaining FAs had no significant effect on the K(d) values of both the AR and ER complexes. According to these priliminary results it is postulated that men should benefit with a diet rich in certain essential polyunsaturated fatty acids although its function remains to be clarified.
Prinsloo
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Wolmarans Research Laboratory, Department of Urology, University of Pretoria, Pretoria, South Africa. smuller@poshllion.up.ac.za
van Aswegen
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CH
D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D005227:Fatty Acids; D013739:Testosterone; D004958:Estradiol