Natural extranuclear androgen receptor ligands as endocrine disruptors of cancer cell growth

Even though the term endocrine disruption primarily designates environmental chemicals that can interfere with the action of hormones, in recent years it has been extended to include also plant derived compounds that can reach the human body, naturally, or have been identified and studied as alternative pharmaceutical agents. In fact, for a large number of them, their antihormonal action was appreciated by different traditional herbal medicines. In the present review we report the majority of the plant derived compounds that exhibit an antiandrogenic effect and the known mechanisms of action. These include a disruption at testosterone production level and at the classical androgen receptor triggered pathways, including membrane initiated ones. Finally, for the first time we describe the possible involvement of alternative cell membrane androgen receptor systems and the lipid signaling disruption by natural androgen, providing hints about a novel class of therapeutic involvement of androgens.