A Combination Of Micronutrients Is Beneficial In Reducing The Incidence Of Prostate Cancer And Increasing Survival In The Lady Transgenic Model

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology
Article Date: 12 Jul 2009 - 0:00 PDT

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UroToday.com - Dietary micronutrients are a common component of people's diet as they seek to prevent cancer and other diseases. Micronutrients protect against cellular oxidative damage by neutralizing oxygen free radicals. In the May 2009 issue of Cancer Prevention Research, Dr. VasundaraVenkateswaran and associates tested the effects and timing of the micronutrients vitamin E (E), selenium (S), and lycopene (L) on the development of prostate cancer (CaP) in the Lady transgenic model.

Transgenic male mice were randomized to the following groups; control diet, or control diet supplemented with a combination of E+S+L started at either 4, 8, 20, or 36 weeks of age. This experiment sought to investigate if the preventive effect of micronutrients was mediated by inhibiting cancer initiation or progression. Another experimental objective was to examine the micronutrients that were essentially contributing to this reduced incidence. To do this, transgenic male mice were randomized at 4 weeks of age to one of the following diets; control diet, control diet with a combination of E+S, and control diet supplemented with a combination of E+S+L. Mice were sacrificed and tissue and blood examined at 58 weeks of age.

Weight gain was similar among groups. At 58 weeks of age there was a significant increase in the survival proportion of the animals in all of the intervention groups compared with the controls. Either E+S or E+S+L or diet supplemented with E+S+L initiated at 8, 20, and 36 weeks of age showed a significant increase in median survival compared with controls. Control mice would not be continued on the diet beyond 48 weeks of age due to tumor burden. Among control mice, 75% developed CaP and 16.7% high grade PIN. Only 10% of mice supplemented at 4 weeks of age with E+S+L developed tumors. Use of E+S+L when commenced by 8 weeks of age resulted in a highly significant reduction in CaP incidence. When micronutrients were commenced at 20 and 36 weeks of age, none of the mice had normal prostates. In control mice, liver metastasis were present in 75%, but in only 10% and 15.4% when micronutrients were started at 4 and 8 weeks, respectively. Early administration of micronutrients resulted in reduced the expression of proliferative marker PCNA and increased the extent of apoptosis. It also altered cell cycle regulation with up-regulation of the prognostic tissue marker p27kip1. Among all histologic, survival and molecular parameters assessed, it was apparent that lycopene was essential to the beneficial outcome.

Despite the negative outcome of the SELECT trial, these data suggest that the early administration of micronutrients is important in experimental models.

Venkateswaran V, Klotz LH, Ramani M, Sugar LM, Jacob LE, Nam RK, Fleshner NE
Cancer Prev Res (Phila Pa). 2009 May;2(5):473-83
10.1158/1940-6207.CAPR-08-0124

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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