Lycopene may act on male hormones to fight cancer

Lycopene, the carotenoid found in tomatoes, may reduce the risk of prostate cancer by inhibiting the male hormone's effect on the prostate, report researchers from DSM this week, writes Dominique Patton.

Their study, carried out on a rat model, is the first to support this mechanism and could be a major breakthrough in understanding the substantial epidemiological evidence linking lycopene to a lower risk of prostate cancer.

Prostate cancer is one of the biggest cancer killers in industrial countries and affects more than 500,000 men worldwide every year. This number is expected to increase with the ageing population.

However studies have shown that men with a high consumption of tomatoes and tomato-based products are less prone to the disease. Men eating four to five tomato based-dishes per week were found to be protected by 25 per cent compared to men eating tomatoes only rarely.

In the study published in the online edition of FASEB (doi:10.1096/fj.03-1116fje) this week, scientists from the leading vitamins firm DSM and the Charité Hospital in Berlin describe how they fed rats lycopene, vitamin E, a combination of both or a placebo mixture for four weeks, and then injected prostate cancer cells into their prostates. These cancer cells grew into tumours in the following two weeks.

Feeding lycopene as well as vitamin E caused an enhanced killing rate of tumor cells, which was shown by larger areas of dead tissue in the prostate tumours.

They then used the new technology 'nutrigenomics' to monitor the expression of thousands of genes in the tumours in order to investigate the molecular mechanisms behind the effect of lycopene and vitamin E on tumour cells.

Their analysis revealed that both nutrients affected gene expression directly in the tumours: lycopene interfered with local androgen activation by down-regulating 5-alpha-reductase, the key enzyme for the transformation of testosterone to its most active form dehydrotestosterone (DHT). As a consequence, the expression of androgen-regulated target genes was also reduced.

In addition, lycopene decreased the expression of two prostatic cytokines, IGF-I and IL-6, both regarded as risk factors for prostate cancer. Vitamin E reduced androgen signaling without affecting androgen metabolism.

These results show that the pure lycopene molecule targets a key mechanism driving prostate cancer development, said the team.

"We had not anticipated finding this mechanism and were thrilled by our results," Karin Wertz, laboratory head at DSM Nutritional Products, told NutraIngredients.com.

"If you want to prevent a disease it is best if you can target the key pathway and it is known that the male sex hormones are the drivers in this disease. We couldn't have found a better mechanism," she added.

Androgens are considered to play a key role in the development of prostate cancer in men over lifetime. Scientists recently reported that a little-known molecule in soy, equol, is also a powerful blocker of the male hormone involved in prostate cancer.

However other lycopene experts have suggested that the carotenoid may work by activating special enzymes that target the body's oxidative response processes.

Wertz suggested that such a mechanism could work alongside lycopene's action on male hormones.

The researchers are hoping that a human trial will prove their findings.