Klin Farmakol Farm. 2005;19(4):211-214

AROMATASE - TARGET OF ANTI-HORMONAL THERAPHY

Petr Hodek, Julie Fidlerová, Marie Stiborová

Univerzita Karlova v Praze, Přírodovědecká fakulta, katedra biochemie, Praha

The most frequent cancer cases include breast and prostate tumors. These occur in tissues exposed to relatively high concentrations of the oestrogens. As oestrogens are known cell proliferators, it might be possible to reduce the risk of this particular cancer as well as to prolong survival of cancer patients by decreasing the oestrogen concentration or its impact. There are two basic ways how to interfere with biosynthesis or oestrogen targets. The first one is based on the reduction of activity of cytochrome P450 (aromatase), the enzyme that catalyses aromatization of androgens resulting in oestrogens, via down – regulation of the enzyme expression or inhibition of the synthesized enzyme. The second approach consists in blocking the oestrogen receptor by its antagonists. Moreover, compounds of clinical relevance for an anti-hormonal therapy are listed including the mechanisms of their action. Recent anti-hormonal therapy is based on application of aromatase inhibitors, drugs belonging to the third generation. Simultaneously tamoxifene an, oestrogen receptor antagonist, is often used for therapy of breast cancer patients as well as an adjuvant agent for women with high risk of this cancer. In the context of anti-hormonal outcome natural compounds having either oestrogenic or anti-oestrogenic effects are mentioned. In case of flavonoids, the structure-function relationship is discussed in detail. Flavons are aromatase inhibitors while highly similar isoflavons act as compounds modulating an oestrogen receptor. Natural compounds are a real “gold mine” the drug design as their structure – junction relationships are being extensively studied.

Keywords: Key words: inhibition, cytochrome P450, aromatase, oestrogen receptor, carcinogenesis, breast cancer.

Published: January 1, 2006  Show citation