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Inositol and inositol hexaphosphate suppress cell proliferation and tumor formation in CD-1 mice
A M Shamsuddin1, A Ullah, A K Chakravarthy
1Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.
Abstract:
In previous studies, we have shown that inositol hexaphosphate (InsP6), a constituent of cereal diet, inhibited azoxymethane-induced experimental large intestinal cancer (LIC) in Fischer 344 rats. We now report a similar antineoplastic action of InsP6 in CD-1 mice injected with 1,2-dimethylhydrazine (DMH). We had hypothesized that InsP6 may bring about this effect by undergoing dephosphorylation to lower phosphorylated forms; the ready availability of Ins, to react with phosphates, may increase the total amount of the lower phosphorylated Ins and potentiate the action of InsP6. LIC induced by DMH (15 mg/kg/week x 13) in mice given a mixture of 1% InsP6 + 1% Ins show a significant reduction (P less than 0.005) in LIC prevalence over InsP6 treatment. Surprisingly, Ins, an in vitro growth promoting agent also caused a significant (P less than 0.001) suppression of LIC. InsP6 +/- Ins also showed a concomitant reduction in the mitotic rate in the non-neoplastic epithelium. Body weight data did not suggest any overt toxic effect of long-term administration of InsP6, Ins or InsP6 + Ins. Since InsP6 is antineoplastic in two species of experimental animals, it should, in combination with Ins, be considered in our strategies for prevention of large intestinal cancer.
Insights
Inositol hexaphosphate (InsP6) and inositol (Ins) significantly reduced large intestinal cancer (LIC) in mice. This combination therapy warrants consideration for future cancer prevention strategies.
Area of Science:
- Oncology
- Nutritional Science
- Gastroenterology
Background:
- Inositol hexaphosphate (InsP6), found in cereal grains, has demonstrated inhibitory effects on experimental large intestinal cancer (LIC) in prior studies.
- Previous research indicated InsP6's antineoplastic properties in Fischer 344 rats against azoxymethane-induced LIC.
Purpose of the Study:
- To investigate the antineoplastic effects of InsP6 in CD-1 mice using 1,2-dimethylhydrazine (DMH) as an inducer.
- To explore the potential synergistic or potentiating effects of combining InsP6 with inositol (Ins) in preventing DMH-induced LIC.
Main Methods:
- CD-1 mice were administered DMH (15 mg/kg/week x 13) to induce LIC.
- Experimental groups received either InsP6, Ins, or a combination of InsP6 + Ins.
- Tumor prevalence and mitotic rates in the non-neoplastic epithelium were assessed.
- Body weight was monitored to evaluate potential toxicity.
Main Results:
- A significant reduction in LIC prevalence was observed in mice treated with the InsP6 + Ins mixture compared to InsP6 alone (P < 0.005).
- Inositol (Ins) alone also demonstrated a significant suppression of LIC (P < 0.001).
- Both InsP6 and Ins, individually or in combination, led to a reduced mitotic rate in the non-neoplastic epithelium.
Conclusions:
- InsP6 exhibits antineoplastic activity against large intestinal cancer in two different species (rats and mice).
- The combination of InsP6 and Ins shows enhanced efficacy in reducing LIC prevalence and mitotic activity.
- InsP6, particularly in combination with Ins, represents a promising strategy for the prevention of large intestinal cancer.