Inositol Hexaphosphate Inhibits Tumor Growth, Vascularity, and Metabolism in TRAMP Mice: A Multiparametric Magnetic Resonance Study
Menée à l'aide d'un modèle murin transgénique d'adénocarcinome de la prostate et à l'aide de l'imagerie par résonance magnétique, cette étude montre que l'inositol hexaphosphate, un composé présent dans l'alimentation riche en fibres, peut inhiber le processus de vascularisation, le métabolisme et la croissance de la tumeur
Herein, employing anatomical and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), we evaluated non-invasively, 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 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 anti-angiogenic 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 (AMPKTh172) 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 utilizing quantitative high-resolution 1H-NMR on prostate tissue extracts showed that IP6 significantly decreased glucose metabolism and membrane phospholipid synthesis, in addition to causing an increase in myo-inositol levels in the prostate. Together, these findings show that oral IP6 supplement blocks PCa growth and angiogenesis in 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.