Potential Role of Estrogen Metabolite 2-Methoxyestradiol in Health and Disease.

ABSTRACT

2-Methoxyestradiol (2-ME2) is an endogenous metabolite of 17β-estradiol (E2) that was originally thought to be an inert end product of estrogen metabolism. However, studies con ducted over the past two decades have shown 2-ME2 to be a promising anticancer agent. Reports suggest that 2-ME2 directly infuences tumor growth through mechanisms which reduce cell proliferation or induce apoptosis as well as through the inhibition of angiogenesis. Incidentally, 2-ME2 as an anticancer agent has poor bioavailability, and this has led to the development of several analogs and derivatives, which currently have had limited success. Thus, it is imperative that we re-evaluate our understanding of 2-ME2-mediated effects in order to innovatively derive, or generate, more effcacious cancer treatment options. In this review, the roles of 2-ME2 in cancer as well as the highly variable mechanisms of action reported for this metabolite are discussed.