Multiple therapeutic and preventive effects of 3,3'-diindolylmethane on cancers including prostate cancer and high grade prostatic intraepithelial neoplasia

Cruciferous vegetables belong to the plant family that has flowers with four equal-sized petals in the pattern of a crucifer cross.These vegetables are an abundant source of dietary phytochemicals,including glucosinolates and their hydrolysis products such as indole-3-carbinol（I3C） and 3,3＇-diindolylmethane（DIM）.By 2013,the total number of natural glucosinolates that have been documented is estimated to be 132.Recently,cruciferous vegetable intake has garnered great interest for its multiple health benefits such as anticancer,antiviral infections,human sex hormone regulation,and its therapeutic and preventive effects on prostate cancer and high grade prostatic intraepithelial neoplasia（HGPIN）.DIM is a hydrolysis product of glucosinolates and has been used in various trials.This review is to provide an insight into the latest developments of DIM in treating or preventing both prostate cancer and HGPIN.

Prediction value of high-grade prostatic intraepithelial neoplasia for prostate cancer on repeat biopsies

Objective: The significance of isolated high-grade prostatic intraepithelial neoplasia in initial biopsy as an predic-tor for prostate cancer has been extensively research, and the true relationship remnant is no clear till now. The aim of this study is to evaluate prediction value of cancer on repeat biopsy in patients with high-grade prostatic intraepithelial neoplasia, using multivariate analysis. Methods: Thirty-eight men with a diagnosis of isolated high-grade prostatic intraepithelial neo-plasia in initial needle biopsy were studies, in the Fist Affiliated Hospital of Medical School of Xi'an Jiaotong University, from January 2003 to March 2009. These samples were using immunostaining of p63 and 34βE12 and P504s, with a median fol-low-up of 525 (range, 7 to 1650) days, and to researched the incidence of subsequent prostate cancer, and to predicted the risk of prostate cancer in clinicopathological parameters of isolated high-grade prostatic intraepithelial neoplasia on repeat biopsies by logistic regression analysis. Results: There were 10 of 38 (26.3%) men with prostate cancer on repeat biopsies after diagnosis isolated high-grade prostatic intraepithelial neoplasia in initial biopsy, of the rates of prostate cancer were 80% for micropapillary and 75% for cribriform high-grade prostatic intraepithelial neoplasia (P < 0.05), respectively. The positive cores of isolated high-grade prostatic intraepithelial neoplasia was the important for the risk of prostate cancer using Multi-factor logistic regression analysis. The time range in 30 to 690 days was stronger risk for prostate cancer detection after diagnosis isolated HGPIN in initial biopsy. p63 and 34βE12 were disrupted positive expression, and P504S was weak posi-tive expression in the 61% isolated high-grade prostatic intraepithelial neoplasia. Conclusion: Isolated high-grade prostatic intraepithelial neoplasia on repeat biopsy conferred a 26.3% risk of prostate cancer, and this risk level is lower than the previ-ously reported risk of 24% to 58%. The number of positive cores and the histopathological pattern with high-grade prostatic intraepithelial neoplasia on initial biopsy was significantly associated with the risk of cancer.

High-dose dietary zinc promotes prostate intraepithelial neoplasia in a murine tumor induction mode

To evaluate the role of high-dose dietary zinc in the process of prostate malignancy,60 Sprague-Dawley rats were randomly divided into four groups：tumor induction with carcinogen and hormone （group 1）,oral zinc administration without tumor induction （group 2）,oral zinc administration with tumor induction （group 3） and a control without zinc administration or tumor induction （group 4）. Zinc was supplied orally in the form of zinc sulfate heptahydrate dissolved in drinking water to groups 2 and 3 for 20 weeks. Although the serum level of zinc measured at 20 weeks was maintained similarly in each group （P = 0.082）,intraprostatic zinc concentrations were statistically different. Group 1 prostates contained the least amount of zinc in both the dorsolateral and ventral lobes at levels of 36.3 and 4.8 μg g^-1,respectively. However,in group 3,zinc levels increased in both lobes to 59.3 and 12.1 μg g^-1,respectively,comparable with that of group 4 （54.5±14.6 and 14.1±2.4 μg g^-1）. In spite of these increases in zinc concentration,the prevalence of prostate intraepithelial neoplasm was rather increased in group 3 （53.3% and 46.7%） compared with group 1 （33.3% and 33.3%） in both dorsolateral and ventral prostate lobes. Although prostate intraepithelial neoplasm did not develop in any prostate in group 4,zinc administration did induce prostate intraepithelial neoplasm in group 2 （46.7% and 40.0%）. Thus,although high dietary zinc increased intraprostatic zinc concentrations,it promoted,instead of preventing,prostate intraepithelial neoplasm in a murine prostate malignancy induction model.