Journal Article

Anti-angiogenic activity of inositol hexaphosphate (IP<sub>6</sub>)

Ivana Vucenik, Antonino Passaniti, Michele I. Vitolo, Kwanchanit Tantivejkul, Paul Eggleton and AbulKalam M. Shamsuddin

in Carcinogenesis

Volume 25, issue 11, pages 2115-2123
Published in print November 2004 | ISSN: 0143-3334
Published online November 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh232
Anti-angiogenic activity of inositol hexaphosphate (IP6)

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A significant anticancer activity of the naturally occurring carbohydrate inositol hexaphosphate (IP6) has been reported against numerous cancer models. Since tumors require angiogenesis for growth and metastasis, we hypothesize that IP6 reduces tumor growth by inhibiting angiogenesis. Because angiogenesis depends on the interaction between endothelial and tumor cells, we investigated the effect of IP6 on both. IP6 inhibited the proliferation and induced the differentiation of endothelial cells in vitro; the growth of bovine aortic endothelial cells (BAECs) evaluated by MTT proliferation assay was inhibited in a dose-dependent manner (IC50 = 0.74 mM). The combination of IP6 and vasostatin, a calreticulin fragment with anti-angiogenic activity, was synergistically superior in growth inhibition than either compound. IP6 inhibited human umbilical vein endothelial cell (HUVEC) tube formation (in vitro capillary differentiation) on a reconstituted extracellular matrix, Matrigel, and disrupted pre-formed tubes. IP6 significantly reduced basic fibroblast growth factor (bFGF)-induced vessel formation (P < 0.01) in vivo in Matrigel plug assay. Exposure of HepG2, a human hepatoma cell line, to IP6 for 8 h, resulted in a dose-dependent decrease in the mRNA levels of vascular endothelial growth factor (VEGF), as assessed by RT–PCR. IP6 treatment of HepG2 cells for 24 h also significantly reduced the VEGF protein levels in conditioned medium, in a concentration-dependent manner (P = 0.012). Thus, IP6 has an inhibitory effect on induced angiogenesis.

Keywords: BAECs, bovine aortic endothelial cells; bFGF, basic fibroblast growth factor; CI, combination index; HIF, hypoxia-inducible factor; HRVT, HUVEC retrovirus telomerized; HUVEC, human umbilical vein endothelial cell; IP6, hexaphosphate; MBP, maltose-binding protein; PDN, P-domain of calreticulin (residues 181–290); PI3K, phosphatidylinositol 3′-kinase; VEGF, vascular endothelial growth factor

Journal Article.  7663 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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