Role of mammalian lignans in the prevention and treatment of prostate cancer.

Prostate cancer is the third most common cancer in men, and its incidence has been increasing by 1.7% per year for the past 15 years.  Existing data strongly suggests that diet may play a central role in the pathogenesis of prostate cancer.  There is an approximately 60-fold difference in incidence rates and a 17-fold difference in mortality rates between the US and China for the disease.  It has been suggested that differences in diet between Eastern and Western cultures is largely responsible for these differences.  Traditional Eastern diets are rich in phytoestrogen compounds, particularly those derived from soy.  However, most cereals, fruits and vegetables are richer in lignan phytoestrogens than any other type of phytoestrogen.  Given the fact that lignans are more widely distributed in food than any other phytoestrogen, the role of these compounds has become the focus of a growing body of research.  The objective of this paper is to review existing evidence on the role of lignans in the prevention and treatment of prostate cancer.

Lignans occur in the highest concentrations in flaxseed, but are also present in most cereals, fruits, and vegetables.  The principle dietary lignans are isolariciresinol, pinoresinol, secoisolariciresinol diglycoside (SDG), secoisolariciresinol, hydroxymatairesinol (HRM), matairesinol glycoside, and matairesinol.  SDG and matairesinol are the main precursors of the mammalian lignans enterolactone and enterdiol, which are the primary lignans observed in biological fluids.  Enterolactone and enterodiol are produced from their plant precursor via Intestinal bacteria.  Other lignans can also be metabolized into enterolactone and enterodiol, but to a lesser degree than SDG and matairesinol. 

In vitro studies reviewed suggest that lignans (plant and mammalian) exert anticancer effects.  However, very few of these studies have used prostate cell lines.  In reviewing the in vitro data, the author’s state that the validity of the reported effects (in vitro) of lignans with regard to prostate cancer requires clarification and support from in vivo studies. 

The in vivo studies reviewed appeared to support in vitro data, reporting a protective effect of lignans on prostate cancer.  All of the animal studies observed a significant decrease in tumor mass following dietary intervention with lignan rich foods.  The few in vivo human studies reviewed reported inconsistent results.  Of the five studies reviewed, two reported a beneficial effect in men consuming a lignan-rich diet, one found no effect with flax and soy consumed together, and the remaining two found no link between serum enterolactone levels and prostate cancer risk.  Additional human studies have reported no association between serum enterolactone levels and prostate cancer risk in men consuming a varied diet. 

A number of discrepancies exist in the in vivo data reviewed in this paper.  A large number of dietary intervention trials used foods rich in lignans, including flaxseed and rye bread.  As such, it is not possible to attribute the in vivo anticancer effects to the lignans alone.  Other bioactive components in the foods may have influenced prostate pathogenesis either on their own or synergistically with the lignans.  Future research is suggested that would specifically focus on the in vitro effects of purified lignans on established prostate cancer cell lines.