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Inositols, especially myo-inositol and inositol hexakisphosphate, have gained significant attention for their biological activities and health benefits. While well-known for their roles in cancer treatment and prevention, they also exhibit properties beneficial for energy metabolism and metabolic disorders. This review highlights their potential roles in decreasing insulin resistance, increasing insulin sensitivity, and enhancing cellular energetics. Despite recent advances, further research is needed to fully understand their effects on metabolism and insulin resistance.

Introduction

Cancer remains one of the world’s major health challenges, with colorectal cancer (CRC) being particularly prevalent. Dietary factors play a crucial role in the incidence of CRC, making natural dietary agents promising for cancer prevention and treatment. Inositol hexakisphosphate (IP6) and myo-inositol are abundant in plants, especially cereals and legumes, and play significant roles in cellular functions. IP6 has shown striking anticancer activity, reducing cell proliferation and inducing apoptosis in malignant cells. The combination of IP6 and myo-inositol has shown enhanced anticancer effects.

Anticancer Activity of IP6

Hypotheses and First Experiments

Initial experiments demonstrated IP6’s ability to reduce colon cancer cell proliferation and induce apoptosis. It was hypothesized that orally administered IP6 would be absorbed, dephosphorylated, and enter the inositol phosphate pool, affecting tumor progression. These hypotheses have been confirmed over the years.

Broad-Spectrum Anticancer Agent

IP6 has shown consistent growth inhibition of various cancer cells in vitro and in vivo, including leukemia, colon, breast, cervical, prostate, and liver cancer cells. It also induces differentiation and maturation of malignant cells. IP6’s cancer-preventive activity has been demonstrated in models of colon, mammary, and skin cancer. Additionally, IP6 has shown therapeutic properties in inhibiting tumor formation and metastasis in experimental models.

Ins Potentiates the Anticancer Activity of IP6

While myo-inositol alone has some anticancer effects, its combination with IP6 enhances these effects. Studies have shown that the combination significantly reduces tumor incidence and improves survival in animal models. Clinical studies have also demonstrated improved outcomes in cancer patients treated with the combination of IP6 and myo-inositol.

Mechanism of Action and Molecular Interactions

IP6 modulates cellular responses by interacting with various molecular targets and signaling pathways. It affects cell proliferation, differentiation, apoptosis, angiogenesis, and metastasis suppression. Key molecular targets include p21, p27, PI3K/Akt pathway, and NF-kappaB. IP6’s antioxidant properties further contribute to its anticancer effects by chelating iron and inhibiting hydroxyl radical formation.

Sensitivity and Selectivity of IP6

IP6 selectively targets cancer cells while protecting normal cells. It has been shown to sensitize cancer cells to chemotherapy while reducing side effects. IP6 acts synergistically with standard chemotherapeutics, improving their efficacy and reducing adverse effects.

Clinical Observations

Clinical studies have shown that IP6 and myo-inositol improve the quality of life and reduce chemotherapy side effects in cancer patients. Observational studies and case reports have demonstrated tumor growth inhibition and regression, enhanced immunity, and better tolerance to chemotherapy.

Conclusions

Inositols, particularly IP6 and myo-inositol, offer promising potential for cancer prevention and treatment. Their roles in energy metabolism and insulin signaling pathways further highlight their therapeutic benefits. More controlled clinical trials are needed to explore their full potential and applications in clinical settings.

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