Herein, employing anatomical and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), we evaluated noninvasively, the in vivo, chemopreventive efficacy of
inositol hexaphosphate (IP6), a major constituent of high-fiber diets, against prostate
tumor growth and progression in transgenic
adenocarcinoma of the mouse prostate (TRAMP) model. Male TRAMP mice, beginning at 4 weeks of age, were fed with 1%, 2%, or 4% (w/v) IP6 in
drinking water or only
drinking water till 28 weeks of age and monitored using MRI over the course of study. Longitudinal assessment of prostate volumes by conventional MRI and
tumor vascularity by
gadolinium-based DCE-MRI showed a profound reduction in
tumor size, partly due to antiangiogenic effects by IP6 treatment. As potential mechanisms of IP6 efficacy, decrease in the expression of
glucose transporter GLUT-4 protein together with an increase in levels of phospho-
AMP-activated kinase (AMPK(Th172)) were observed in prostate tissues of mice from IP6 fed-groups, suggesting that IP6 is interfering with the metabolic events occurring in TRAMP prostate. Investigative metabolomics study using quantitative high-resolution (1)H-NMR on prostate
tissue extracts showed that IP6 significantly decreased
glucose metabolism and membrane
phospholipid synthesis, in addition to causing an increase in
myoinositol levels in the prostate. Together, these findings show that oral IP6 supplement blocks growth and angiogenesis of
prostate cancer in the TRAMP model in conjunction with metabolic events involved in
tumor sustenance. This results in energy deprivation within the
tumor, suggesting a practical and translational potential of IP6 treatment in suppressing growth and progression of
prostate cancer in humans.