title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado, USA.
authors.forename: Rana P
authors.initials: RP
authors.lastname: Singh
authors.forename: Girish
authors.initials: G
authors.lastname: Sharma
authors.forename: G U
authors.initials: GU
authors.lastname: Mallikarjuna
authors.forename: Sivanandhan
authors.initials: S
authors.lastname: Dhanalakshmi
authors.forename: Chapla
authors.initials: C
authors.lastname: Agarwal
authors.forename: Rajesh
authors.initials: R
authors.lastname: Agarwal
mesh_terms: D000821:Animal Feed; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010833:Phytic Acid / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D010833:Phytic Acid