Anti-cancer activity of the bioactive compound inositol pentakisphosphate
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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. © 2009 Springer Science+Business Media B.V.
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A novel inhibitor of the PI3K/Akt pathway based on the structure of inositol 1,3,4,5,6-pentakisphosphateFalasca, Marco; Chiozzotto, D.; Godage, H.; Mazzoletti, M.; Riley, A.; Previdi, S.; Potter, B.; Broggini, M.; Maffucci, T. (2010)Background: Owing to its role in cancer, the phosphoinositide 3-kinase (PI3K)/Akt pathway is an attractive target for therapeutic intervention. We previously reported that the inhibition of Akt by inositol 1,3,4,5,6- ...
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