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Inositol hexaphosphate and inositol inhibit DMBA-induced rat mammary cancer
I Vucenik1, G Y Yang, A M Shamsuddin
1Department of Medical and Research Technology, University of Maryland School of Medicine, Baltimore 21201-1192, USA.
Abstract:
Because inositol hexaphosphate (InsP6) and inositol (Ins), contained in plants and most mammalian cells, have been demonstrated to have anti-cancer and anti-cell proliferative action in several experimental models of carcinogenesis we have examined the effect of InsP6 +/- Ins on DMBA-induced rat mammary tumor model. Starting two weeks prior to induction with DMBA, the drinking water of female Sprague-Dawley rats was supplemented with either: 15 mM InsP6, 15 mM Ins, or 15 mM InsP6 + 15 mM Ins; a control group received no inositol compounds. Animals (49-day-old) were given a single intragastric dose of DMBA (5 mg/rat) in 1 ml of corn oil administered by oral intubation. After 45 weeks of treatment, the animals in all the three treatment regimens showed a significant reduction (P < 0.05) in tumor incidence. Tumor number, multiplicity and tumor burden were also significantly (P < 0.05) reduced by InsP6 +/- Ins. When all the parameters were taken into consideration, the best results were obtained by the combination treatment of InsP6 + Ins. Four additional groups not receiving DMBA, but drinking tap water, InsP6, Ins, or InsP6 + Ins of the same molarity as experimental groups were observed for the duration of the study to monitor for any toxicity following this long-term treatment; no significant toxicity as evaluated by body weight gain, serum and bone mineral levels was detected. We demonstrate that InsP6 +/- Ins reproducibly inhibits experimental mammary carcinoma, therefore having great potential as a chemopreventive and adjuvant therapeutic agent for this disease as well.
Insights
Inositol hexaphosphate (InsP6) and inositol (Ins) significantly reduced mammary tumors in a rat model. The combination of InsP6 and Ins showed the best results, with no observed toxicity, indicating potential for cancer prevention and treatment.
Area of Science:
- Oncology
- Nutritional Biochemistry
- Carcinogenesis Research
Background:
- Inositol hexaphosphate (InsP6) and inositol (Ins) are naturally occurring compounds with demonstrated anti-cancer properties.
- Previous studies suggest these compounds possess anti-cell proliferative actions in various carcinogenesis models.
Purpose of the Study:
- To investigate the chemopreventive and therapeutic potential of InsP6 and Ins in a DMBA-induced rat mammary tumor model.
- To evaluate the efficacy of individual and combined InsP6 and Ins treatments on mammary carcinoma development.
Main Methods:
- Female Sprague-Dawley rats were administered DMBA to induce mammary tumors.
- Rats received supplemented drinking water with 15 mM InsP6, 15 mM Ins, or a combination of both, starting two weeks prior to DMBA induction.
- Tumor incidence, number, multiplicity, and burden were assessed over 45 weeks. Toxicity was evaluated through body weight, serum, and bone mineral levels.
Main Results:
- All treatment groups (InsP6, Ins, InsP6 + Ins) showed a significant reduction in tumor incidence (P < 0.05).
- Tumor number, multiplicity, and burden were significantly decreased by InsP6 and Ins treatments.
- The combination of InsP6 + Ins yielded the most favorable outcomes.
- No significant toxicity was observed in any treatment group, even with long-term administration.
Conclusions:
- InsP6 and Ins, individually and in combination, effectively inhibit experimental mammary carcinoma in rats.
- The combination of InsP6 and Ins demonstrated superior efficacy without adverse effects.
- These findings highlight the significant potential of InsP6 and Ins as chemopreventive and adjuvant therapeutic agents for mammary cancer.