Inositol Hexaphosphate and Inositol Inhibit Colorectal Cancer Metastasis to the Liver in BALB/c Mice

Abstract

Inositol hexaphosphate (IP6) and inositol (Ins), naturally occurring carbohydrates present in most mammals and plants, inhibit the growth of numerous cancers both in vitro and in vivo. In this study, we first examined the anti-metastatic effects of IP6 and Ins using a liver metastasis model of colorectal cancer (CRC) in BALB/c mice. CT-26 cells were injected into the splenic capsule of 48 BALB/c mice. The mice were then randomly divided into four groups: IP6, Ins, IP6 + Ins and normal saline control (n = 12 per group). IP6 and/or Ins (80 mg/kg each, 0.2 mL/day) were injected into the gastrointestinal tracts of the mice on the second day after surgery. All mice were sacrificed after 20 days, and the tumor inhibition rates were determined. The results demonstrated that the tumor weights of liver metastases and the tumor inhibition rates were reduced in the experimental groups compared to the control group and that treatment with the combination of IP6 and Ins resulted in greater inhibition of tumor growth than treatment with either compound alone. These findings suggest that IP6 and Ins prevent the development and metastatic progression of colorectal cancer to the liver in mice by altering expression of the extracellular matrix proteins collagen IV, fibronectin and laminin; the adhesion factor receptor integrin-β1; the proteolytic enzyme matrix metalloproteinase 9; and the angiogenic factors vascular endothelial growth factor, basic fibroblast growth factor, and transforming growth factor beta in the tumor metastasis microenvironment. In conclusion, IP6 and Ins inhibited the development and metastatic progression of colorectal cancer to the liver in BALB/c mice, and the effect of their combined application was significantly greater than the effect of either compound alone. This evidence supports further testing of the combined application of IP6 and Ins for the prevention of colorectal cancer metastasis to the liver in clinical studies.

Glycerophosphodiester phosphodiesterase 1 (GDE1) acts as a potential tumor suppressor and is a novel therapeutic target for non-mucin-producing colon adenocarcinoma

“…A possible explanation for this observation is that lower expression of GDE1 converted to less inositol, with less inositol resulting in poorer prognosis. Previous studies have indicated that increasing concentrations of inositol in vivo and in vitro may control cancer metastases and improve quality of life (Bacić et al, 2010;Vucenik & Shamsuddin, 2003;Vucenik & Shamsuddin, 2006;Lam et al, 2006;Abul Kalam, Shamsuddin & Ivana, 2005;Shamsuddin, Ullah & Chakravarthy, 1989;Carlomagno & Unfer, 2011;Fu et al, 2016;Nishino et al, 1999). Supporting evidence for this comes from our survival analysis results, in which higher expression of GDE1 showed better survival in COAD.…”

Identification of differential metabolic characteristics between tumor and normal tissue from colorectal cancer patients by gas chromatography–mass spectrometry

“…It has been reported that inositol hexaphosphate and inositol can inhibit chemically induced rat hepatocarcinogenesis (Lee, Lee, & Choi, ). As the backbone and precursor of inositol phosphates, inositol is primarily used to treat diabetes (Dang, Mukai, Yoshida, & Ashida, ), hepatitis (Okazaki, Setoguchi, & Katayama, ), polycystic ovary syndrome (Santamaria et al, ), colorectal cancer (Fu, Song, Wen, Lu, & Cui, ) and other diseases. Inositol exhibits moderate anticancer activity, and it synergistically enhances the inhibitory effects of inositol hexaphosphate on the growth of colon (Shamsuddin, Ullah, & Chakravarthy, ) and mammary cancers (Vucenik, Yang, & Shamsuddin, ).…”

<p>Combination of Inositol Hexaphosphate and Inositol Inhibits Liver Metastasis of Colorectal Cancer in Mice Through the Wnt/β-Catenin Pathway</p>

“…25 Furthermore, another study in our laboratory established a BALB/c mouse model of colorectal cancer with liver metastasis by injecting the cell line into spleen; results showed that colorectal cancer with liver metastasis could be inhibited in this model when IP6 is combined with INS. 26 This model mimics the vascular diffusion process of colorectal cancer; this process is a characteristic of colorectal cancer with liver metastasis.…”