Study: Inositol efficacy against prostate cancer tumor growth

December 6, 2009

Chemopreventive Efficacy of Inositol Hexaphosphate against

Prostate Tumor Growth and Progression in TRAMPMice

Komal Raina,1Subapriya Rajamanickam,1Rana P. Singh,1,3 and Rajesh Agarwal1,2

Abstract Purpose: Herein, for the first time, we evaluated the in vivo chemopreventive efficacy of inositol hexaphosphate (IP6), a major constituent ofh igh-fiber diets, against prostate tumor growth and progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP)

model.

Experimental Design: Beginning at 4 weeks ofa ge, maleTRAMP micewere fed 2% (w/v) IP6 in drinking water or only drinking water till 24 weeks ofa ge, and then sacrificed. Prostate tissue was subjected to histopathologic analysis and to immunohistochemical analyses for proliferation

and apoptosis.

Results: IP6 feeding did not show any adverse effect on fluid and diet consumption and body weight. There was a significant reduction (40%; P < 0.01) in lower urogenital tract weight in IP6-fedmice. IP6 inhibited prostate cancer progression at prostatic intraepithelial neoplasia stage and strongly reduced the incidence ofa denocarcinoma (prostatic intraepithelial neoplasia/ adenocarcinoma, 75:25% in the IP6 group versus 39:61% in the control group; P < 0.05). The incidences of well-differentiated and poorly differentiated adenocarcinomas in the IP6-fed group were reduced by 44% and 62%, respectively. Immunohistochemical analysis ofpr ostate tissue showed a 26% decrease (P < 0.05) in proliferation cell nuclear antigen ^ positive cells and a 3.5-fold increase in apoptotic cells with no effect on Tag expression by IP6.

Conclusions: These findings are both novel and highly significant in establishing for the first time that oral IP6, without any toxicity, suppresses prostate tumor growth and progression at the neoplastic stage, thereby reducing the incidence ofad enocarcinoma through its antiproliferative and proapoptotic effects, and thus indicating that IP6 could have potential chemopreventive effects against human prostate cancer.

www.aacrjournals.org Clin Cancer Res 3177 2008;14(10)May 15, 2008