**4. Resveratrol**

294 Cancer Prevention – From Mechanisms to Translational Benefits

were required to reduce growth, possibly through alterations in the cell cycle (Ford et al.,

Athymic mice models used by Yang et al., (2011) show strong inhibition of PC3 xenograft growth by high doses of lycopene (16 mg/kg), possibly via increased levels of insulin-like growth factor-binding protein 3, or a reduction in plasma vascular endothelial growth factor (VEGF) levels. In a provocative study of androgen expressing prostate cancer cell lines treated with serum from rats fed a control diet, or diets supplemented with red, or yellow tomato (containing no lycopene), connexin43 (a protein regulating cell growth) was upregulated by both the red and yellow tomato supplemented diet (Gitenay et al., 2007). This suggests tomato compounds other than lycopene may have a role in reducing prostate cancer cell growth; one such candidate might be FruHis, a carbohydrate derivative found in tomato products (Mossine et al., 2008). However, in humans at least, dietary lycopene has been shown to affect gene expression, regardless of whether it is included in its food matrix

In a transgenic mouse model, early intervention with selenium, vitamin E and lycopene supplements was able to significantly reduce prostate cancer and liver metastases (Venkateswaran et al, 2009). Limpens et al., (2006) had earlier reached the same conclusion, but they did not see any activity from the single agents. Naturally, it is difficult to know how much the additional supplements contributed to prostate cancer control, though both groups suggest the combination was important. Not all data are supportive of the growth inhibitory effect of lycopene however, possibly because of differences in the rat model used

Mills et al., (1989), through the Seventh Day Adventist men study, showed a link between low prostate cancer risk and frequent tomato consumption, along with beans, lentils and peas, raisins, dates, and other dried fruit. Giovannucci et al., (2007) performed an analysis on data from the Health Professionals study and found that higher tomato sauce (assumed to be lycopene) intake correlated inversely with prostate cancer incidence; indeed, this was only one of four factors (in addition to African American race, positive family history, and alpha-linolenic acid intake) that predicted for incidence and advanced prostate cancer.

In a small, randomized trial of 30mg lycopene supplementation over 3 weeks prior to prostatectomy, margin positivity at surgery was reduced by lycopene, though no other endpoints were affected (Kucuk et al., 2001). The study was extremely small, and no

Zhang et al., (2010) recently reported a study in 41 men with localized prostate cancer given 10mg lycopene once a day. Seventy percent of men had a reduced slope of PSA rise, and 21% had a decrease in their PSA levels. However, scant details were available for the study, and we do not know whether there were confounding variables; further, this would appear to be the same patient population as in a previous publication (Barber et al., 2006). In a study of 41 men with localised prostate cancer (Barber et al., 2006) given 20 mg lycopene daily, nearly 70% of patients had a slower rate of PSA rise post-treatment. A study in 20

2011).

**3.3** *In vivo* **data** 

(Talvas et al., 2010)

by Imaida et al., (2001).

conclusions can be drawn.

**3.4 Clinical studies in prostate cancer** 

Resveratrol is a phytoalexin found in the skins and seeds of red grapes V*itaceaea vinifera.* Therefore, red wines are especially rich in resveratrol, as is grape juice (Romero-Perez, 1999). Other sources include lentils (as resveratrol-3-O-glucoside), peanuts, dark chocolate and berries (Neveu, 2010).
