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Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):244-50.

In vivo suppression of hormone-refractory prostate cancer growth by inositol hexaphosphate: induction of insulin-like growth factor binding protein-3 and inhibition of vascular endothelial growth factor.

Author information

1
Department of Pharmaceutical Sciences, University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado, USA.

Abstract

PURPOSE:

Diet composition is an important etiologic factor in prostate cancer (PCA) growth and has significant impact on clinical PCA appearance. Because inositol hexaphosphate (IP6) is a dietary phytochemical present in cereals, soy, legumes, and fiber-rich foods, we evaluated efficacy of IP6 against PCA growth and associated molecular events.

EXPERIMENTAL DESIGN:

DU145 cells were injected into nude mice, and animals were fed normal drinking water or 1 or 2% IP6 in drinking water for 12 weeks. Body weight, diet, water consumption, and tumor sizes were monitored. Tumors were immunohistochemically analyzed for proliferating cell nuclear antigen, terminal deoxynucleotidyl transferase-mediated nick end labeling, and CD31. Tumor-secreted insulin-like growth factor binding protein (IGFBP)-3 and vascular endothelial growth factor (VEGF) were quantified in plasma by ELISA.

RESULTS:

IP6 feeding resulted in suppression of hormone-refractory human prostate tumor growth without any adverse effect on body weight gain, diet, and water consumption during entire study. At the end of study, tumor growth inhibition by 1 and 2% IP6 feeding was 47 and 66% (P = 0.049-0.012) in terms of tumor volume/mouse and 40 and 66% (P = 0.08-0.003) in terms of tumor weight/mouse, respectively. Tumor xenografts from IP6-fed mice showed significantly (P < 0.001) decreased proliferating cell nuclear antigen-positive cells but increased apoptotic cells. Tumor-secreted IGFBP-3 levels were also increased up to 1.7-fold in IP6-fed groups. Additionally, IP6 strongly decreased tumor microvessel density and inhibited tumor-secreted VEGF levels.

CONCLUSIONS:

IP6 suppresses hormone-refractory PCA growth accompanied by inhibition of tumor cell proliferation and angiogenesis and increased apoptosis. IP6-caused increase in IGFBP-3 and decrease in VEGF might have a role in PCA growth control.

PMID:
14734476
[Indexed for MEDLINE]
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