Modulation of Aromatase by Phytoestrogens

Abstract

The aromatase enzyme catalyzes the conversion of androgens to estrogens in many human tissues. Estrogens are known to stimulate cellular proliferation associated with certain cancers and protect against adverse symptoms during the peri- and postmenopausal intervals. Phytoestrogens are a group of plant derived naturally occurring compounds that have chemical structures similar to estrogen. Since phytoestrogens are known to be constituents of animal/human food sources, these compounds have received increased research attention. Phytoestrogens may contribute to decreased cancer risk by the inhibition of aromatase enzyme activity and CYP19 gene expression in human tissues. This review covers (a) the aromatase enzyme (historical descriptions on function, activity, and gene characteristics), (b) phytoestrogens in their classifications and applications to human health, and (c) a chronological coverage of aromatase activity modulated by phytoestrogens from the early 1980s to 2015. In general, phytoestrogens act as aromatase inhibitors by (a) decreasing aromatase gene expression, (b) inhibiting the aromatase enzyme itself, or (c) in some cases acting at both levels of regulation. The findings presented herein are consistent with estrogen's impact on health and phytoestrogen's potential as anticancer treatments, but well-controlled, large-scale studies are warranted to determine the effectiveness of phytoestrogens on breast cancer and age-related diseases.

Figure 1

The chemical structure of 17β-estradiol, the most potent sex steroid hormone in the body, with carbon-3 indicated by ● and carbon-17 indicated by ▲, displays the functional groups associated with its biological activity; 4-hydroxyandrostenedione, one of the first aromatase inhibitors used in clinical trials; genistein, a phytoestrogen of the isoflavonoid class, and; anastrozole, a current pharmaceutical agent used as an aromatase inhibitor.

Figure 2

Classification and chemical structure of major classes of phytoestrogens.

Figure 3

Mechanisms of aromatase inhibition (gene expression and enzyme activity) by phytoestrogens.