Anti-cancer activity of the bioactive compound inositol pentakisphosphate

Abstract

Bioactive compounds are extra nutritional constituents found in small quantities in foods. We have recently shown that a bioactive compound, inositol pentakisphosphate (IP₅), a naturally occurring substance that is present in most legumes, wheat bran and nuts, inhibits cell growth of ovarian, lung and breast cancer cells. We demonstrated that IP₅ specifically blocks the activation of the critical phosphoinositide 3-kinase (PI3K) effector Akt, a serine/threonine kinase which plays a key role in different intracellular processes such as cell survival and proliferation. Due to its role in cancer development and progression, the PI3K/Akt pathway is an attractive target for therapeutic intervention. Interestingly, IP₅ possesses anti tumour activity in mice to the same extent than cytotoxic drug cisplatin. Furthermore, IP₅ enhances the effect of cytotoxic drugs in ovarian and lung cancer cells. These results support a role for IP₅ as an anti-tumour agent that may sensitise cancer cells to the action of commonly used anti-cancer drugs. In addition we have recently observed that specific modifications of the IP₅ structure may result in compounds with the same solubility and lack of toxicity in vivo but broader range of action and a higher activity compared to parental molecule indicating that IP₅ may represents a promising molecule for further development of novel anticancer drugs. Therefore, our study reveals a new pharmacologically active nutrient (nutraceutical) as a potential chemopreventive agent and a lead compound for possible development of potent small molecule PI3K/Akt inhibitors.