Phytochemistry Reviews

, Volume 8, Issue 2, pp 369–374 | Cite as

Anti-cancer activity of the bioactive compound inositol pentakisphosphate

Article
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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.

Keywords

Bioactive compounds Inositol polyphosphates Nutraceutical Phosphoinositide 3-kinase 
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Notes

Acknowledgements

This work was supported by FP6 (contract 037344), American Institute for Cancer Research and Fondazione Carichieti.

References

  1. Awad AB, Chan KC, Downie AC, Fink CS (2000) Peanuts as a source of beta-sitosterol, a sterol with anticancer properties. Nutr Cancer 36:238–241. doi: 10.1207/S15327914NC3602_14 PubMedCrossRefGoogle Scholar
  2. Berrie CP, Falasca M (2000) Patterns within protein/polyphosphoinositide interactions provide specific targets for therapeutic intervention. FASEB J 14:2618–2622. doi: 10.1096/fj.00-0096hyp PubMedCrossRefGoogle Scholar
  3. Chang HW, Aoki M, Fruman D, Auger KR, Bellacosa A, Tsichlis PN, Cantley LC, Roberts TM, Vogt PK (1997) Transformation of chicken cells by the gene encoding the catalytic subunit of PI3 Kinase. Science 276:1848–1850. doi: 10.1126/science.276.5320.1848 PubMedCrossRefGoogle Scholar
  4. Chen Q (2004) Determination of phytic acid and inositol pentakisphosphates in foods by high-performance ion chromatography. J Agric Food Chem 52:4604–4613. doi: 10.1021/jf035294x PubMedCrossRefGoogle Scholar
  5. Clark AS, West K, Streicher S, Dennis PA (2002) Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther 1:707–717PubMedGoogle Scholar
  6. Fassina G, Vene R, Morini M, Minghelli S, Benelli R, Noonan DM, Albini A (2004) Mechanisms of inhibition of tumour angiogenesis and vascular tumour growth by epigallocatechin-3-gallate. Clin Cancer Res 10:4865–4873. doi: 10.1158/1078-0432.CCR-03-0672 PubMedCrossRefGoogle Scholar
  7. Ferry S, Matsuda M, Yoshida H, Hirata M (2002) Inositol hexakisphosphate blocks tumour cell growth by activating apoptotic machinery as well as by inhibiting the Akt/NFkappaB-mediated cell survival pathway. Carcinogenesis 23:2031–2041. doi: 10.1093/carcin/23.12.2031 PubMedCrossRefGoogle Scholar
  8. Frontela C, Martínez C, Perez D, Ros G (2004) Phytic acid and inositol phosphates in infant cereal flours: the effect of processing. Abstract 99E-10, IFT Annual Meeting, Las Vegas, NVGoogle Scholar
  9. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275:218–220. doi: 10.1126/science.275.5297.218 PubMedCrossRefGoogle Scholar
  10. Jiang R, Manson JE, Stampfer MJ, Liu S, Willett WC, Hu FB (2002) Nut and peanut butter consumption and risk of type 2 diabetes in women. JAMA 288:2554–2560. doi: 10.1001/jama.288.20.2554 PubMedCrossRefGoogle Scholar
  11. Khwaja A, Rodriguez-Viciana P, Wennstrom S, Warne PH, Downward J (1997) Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway. EMBO J 16:2783–2793. doi: 10.1093/emboj/16.10.2783 PubMedCrossRefGoogle Scholar
  12. Kris-Etherton PM, Zhao G, Binkoski AE, Coval SM, Etherton TD (2001) The effects of nuts on coronary heart disease risk. Nutr Rev 59:103–111PubMedCrossRefGoogle Scholar
  13. Kris-Etherton PM, Hecker KD, Bonanome A, Coval SM, Binkoski AE, Hilpert KF, Griel AE, Etherton TD (2002) Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am J Med 113:71S–88S. doi: 10.1016/S0002-9343(01)00995-0 PubMedCrossRefGoogle Scholar
  14. LeCorre L, Chalabi N, Delort L, Bignon Y-J, Bernard-Gallon DJ (2005) Resveratrol and breast cancer chemoprevention: molecular mechanisms. Mol Nutr Food Res 49:462–471. doi: 10.1002/mnfr.200400094 CrossRefGoogle Scholar
  15. Li D, Yee JA, McGuire MH, Murphy PA, Yan L (1999) Soybean isoflavones reduce experimental metastasis in mice. J Nutr 129:1075–1078PubMedGoogle Scholar
  16. Luo J, Manning BD, Cantley LC (2003) Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 4:257–262. doi: 10.1016/S1535-6108(03)00248-4 PubMedCrossRefGoogle Scholar
  17. Maffucci T, Piccolo E, Cumashi A, Iezzi M, Riley AM, Saiardi A, Godage HY, Rossi C, Broggini M, Iacobelli S, Potter BV, Innocenti P, Falasca M (2005) Inhibition of the phosphatidylinositol 3-kinase/Akt pathway by inositol pentakisphosphate results in antiangiogenic and antitumour effects. Cancer Res 65:8339–8349. doi: 10.1158/0008-5472.CAN-05-0121 PubMedCrossRefGoogle Scholar
  18. Maguire LS, O’Sullivan SM, Galvin K, O’Connor TP, O’Brien NM (2004) Fatty acid profile, tocopherol, squalene and phytosterol content of walnuts, almonds, peanuts, hazelnuts and the macadamia nut. Int J Food Sci Nutr 55:171–178. doi: 10.1080/09637480410001725175 PubMedCrossRefGoogle Scholar
  19. Ng SS, Tsao MS, Nicklee T, Hedley DW (2001) Wortmannin inhibits pkb/akt phosphorylation and promotes gemcitabine antitumour activity in orthotopic human pancreatic cancer xenografts in immunodeficient mice. Clin Cancer Res 7:3269–3275PubMedGoogle Scholar
  20. Piccolo E, Vignati S, Maffucci T, Innominato PF, Riley AM, Potter BV, Pandolfi PP, Broggini M, Iacobelli S, Innocenti P, Falasca M (2004) Inositol pentakisphosphate promotes apoptosis through the PI3K/Akt pathway. Oncogene 23:1754–1765. doi: 10.1038/sj.onc.1207296 PubMedCrossRefGoogle Scholar
  21. Razzini G, Berrie CP, Vignati S, Broggini M, Mascetta G, Brancaccio A, Falasca M (2000) Novel functional PI3 Kinase antagonists inhibit cell growth and tumourigenicity in human cancer cell lines. FASEB J 14:1179–1187PubMedGoogle Scholar
  22. Sanders TH, McMichael RW Jr, Hendrix KW (2000) Occurrence of resveratrol in edible peanuts. J Agric Food Chem 48:1243–1246. doi: 10.1021/jf990737b PubMedCrossRefGoogle Scholar
  23. Shayesteh L, Lu Y, Kuo WL, Baldocchi R, Godfrey T, Collins C, Pinkel D, Powell B, Mills GB, Gray JW (1999) PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 21:99–102. doi: 10.1038/5042 PubMedCrossRefGoogle Scholar
  24. Stacewicz-Sapuntzakis M, Bowen PE (2005) Role of lycopene and tomato products in prostate health. Biochim Biophys Acta 1740:202–205PubMedGoogle Scholar
  25. Stein RC (2001) Prospects for phosphoinositide 3-kinase inhibition as a cancer treatment. Endocr Relat Cancer 8:237–248. doi: 10.1677/erc.0.0080237 PubMedCrossRefGoogle Scholar
  26. Thompson JE, Thompson CB (2004) Putting the rap on Akt. J Clin Oncol 22:4217–4226. doi: 10.1200/JCO.2004.01.103 PubMedCrossRefGoogle Scholar
  27. Ulrich S, Nolter F, Stein JM (2005) Molecular mechanisms of the chemopreventive effects of resveratrol and its analogs in carcinogenesis. Mol Nutr Food Res 49:452–461. doi: 10.1002/mnfr.200400081 PubMedCrossRefGoogle Scholar
  28. Valentiner U, Fabian S, Schumacher U, Leathem AJ (2003) The influence of dietary lectins on the cell proliferation of human breast cancer cell lines in vitro. Anticancer Res 23:1197–1206PubMedGoogle Scholar
  29. Vucenik I, Shamsuddin AM (2003) Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic. J Nutr 133:3778S–3784SPubMedGoogle Scholar
  30. West KA, Castillo SS, Dennis PA (2002) Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resist Updat 5:234–248. doi: 10.1016/S1368-7646(02)00120-6 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Inositide Signalling Group, Centre for Diabetes and Metabolic Medicine, Institute of Cell and Molecular Science, Barts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUK

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