In Vitro Regulation of Cell Growth and Angiogenesis by Inositol Hexaphosphate in Bladder Cancer

Abstract

Background: Inositol Hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is found in food sources high in fiber content. We hypothesized that IP6 would inhibit the cell growth rate of bladder cancer in vitro. Methods: T24 and TCCSUP bladder cancer cell lines were treated with titrating doses of IP6 (0.3, 0.6 and 0.9 mM/well). Cell viability and vascular endothelial growth factor levels were measured. Results: Significant reductions (p < 0.001) in cellular growth were noted in both cell lines at all doses and time points tested, with the exception of 0.3 mM IP6 at 24 hours in the T24 cell line. The percent inhibition of vascular endothelial growth factor was significantly higher than that observed in the TCCSUP cell line at 48 and 72 hours with 0.3 mM IP6 (p < 0.001). The T24 cells exhibited the same level of inhibition at 24 and 48 hours with 0.6 m<smlcap>M</smlcap> dose of IP6 and at 72 hours with the 0.3 mM dose (p < 0.001). Conclusions: In vitro treatment of bladder cancer with the common dietary polyphosphorylated carbohydrate IP6 significantly decreased cellular growth by anti-angiogenic mechanisms. We feel that this data warrants further investigation and consideration for initiation of clinical trials to evaluate the safety and clinical utility of this agent.

Regulation of MicroRNA-155 and Its Related Genes Expression by Inositol Hexaphosphate in Colon Cancer Cells

“…However, IP6 is best appreciated for its anti-cancer properties, resulting from its capability of reduction cell proliferation, apoptosis induction, and tumor metastasis inhibition [8,9,10]. The outcomes of many experiments have shown that IP6 broad spectrum activities involve its impact on various intracellular signaling pathways, such as PI3K/AKT (Phosphatidylinositol-3 Kinase/AKT Serine/Threonine Kinase 1) [11,12] and expression of genes encoding key cellular proteins like p53, p21, p27, BCL-2, and MMPs [13,14,15,16,17,18,19]. The anti-cancer properties of dietary IP6 have previously been demonstrated by both in vitro and in vivo experimental cancer models including, prostate, breast, bladder, and colon [10,12,13,15,16,19].…”

Cellular and Molecular Activities of IP6 in Disease Prevention and Therapy

“…A plethora of studies have investigated the anti-cancer properties of IP6 [ 56 , 57 , 58 ] ( Table 1 ). IP6 and its derivatives, such as IP5, IP4, and IP3, have been shown to possess anti-cancer activities by modulating biological processes implicated in various cancers, including inflammation, apoptosis, angiogenesis, proliferation, cell signaling, and gene expression [ 31 , 113 , 114 ]. Some studies have highlighted the potential cytostatic and cytotoxic properties of IP6 in malignant cells [ 59 , 115 , 116 ] ( Table 1 ).…”

Signalling Properties of Inositol Polyphosphates

“…The potential beneficial effects of exogenous IPs in cancer might go beyond their inhibition of PIs-mediated processes. For instance, Ins P 6 has been reported to have anti-cancer activity in several in vitro and in vivo models [ 65 ], including prostate [ 66 , 67 , 68 ], breast [ 69 , 70 ], bladder [ 71 ] and colon [ 72 , 73 ] cancer. Some very preliminary clinical results are also appearing [ 65 ].…”