IP 6 (inositol hexaphosphate) as a signaling molecule

Current Signal Transduction Therapy

Volumn 7, Issue 3, 2012, Pages 289-304

  Shamsuddin, Abul Kalam ^a   Bose, Sanchita ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

Author keywords

Inositol; IP6; Nutraceuticals; Phytate; Polyphosphates; Signal transduction

Indexed keywords

ADENOSINE TRIPHOSPHATE; CHOLESTEROL; DNA; FIBROBLAST GROWTH FACTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INOSITOL 1,3,4,5 TETRAKISPHOSPHATE; INOSITOL 1,4,5 TRISPHOSPHATE RECEPTOR; INOSITOL POLYPHOSPHATE; IRINOTECAN; MANNOSE 6 PHOSPHATE; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE; PHYTIC ACID; PROTEIN KINASE C; RAS PROTEIN; RNA; SOMATOMEDIN B; SYNDECAN 4; TAMOXIFEN; TRANSCRIPTION FACTOR AP 1;

ABSENCE OF SIDE EFFECTS; ACTINOBACTERIA; ANTIOXIDANT ACTIVITY; APOPTOSIS; ARTICLE; BINDING AFFINITY; BREAST CANCER; CALCIFICATION; CANCER PREVENTION; CARDIOVASCULAR DISEASE; CELL CYCLE REGULATION; CELL DIFFERENTIATION; CELL PROLIFERATION; CHROMATIN ASSEMBLY AND DISASSEMBLY; COLON TUMOR; COLORECTAL CANCER; DIABETES MELLITUS; DNA REPAIR; ENDOCYTOSIS; ENZYME ACTIVATION; EUKARYOTE; EXOCYTOSIS; GERMINATION; HOMEOSTASIS; HUMAN; HYPERLIPIDEMIA; IMMUNE SYSTEM; IN VITRO STUDY; IN VIVO STUDY; LIVER METASTASIS; LUNG METASTASIS; MAMMAL CELL; NEPHROLITHIASIS; NONHUMAN; PLANT; PRIORITY JOURNAL; PROKARYOTE; PROTEIN MOTIF; RNA EDITING; RNA TRANSPORT; SACCHAROMYCES CEREVISIAE; SEED DEVELOPMENT; SIGNAL TRANSDUCTION; THROMBOCYTE;

EID: 84867164960     PISSN: 15743624     EISSN: None     Source Type: Journal    
DOI: 10.2174/157436212802481628     Document Type: Article

References (199)

1. Bozsik A, Kokeny S, Olah E. Molecular mechanisms for the antitumor activity of inositol hexakisphosphate (IP6). Cancer Genom Proteom 2007;4:43-51. (Pubitemid 46426646)
2. Tan X, Calderon-Villalobos LI, Sharon M, et al. Mechanism of auxin perception by the TIR1 ubiquitin ligase. Nature 2007;446:640-5. (Pubitemid 46606890)
3. Draskovic P, Saiardi A, Bhandari R, et al. Inositol hexakisphosphate kinase products contain diphosphate and triphosphate groups. Chem Biol 2008;15:274-86. (Pubitemid 351381988)
4. Bennett M, Onnebo SM, Azevedo C, Saiardi A. Inositol pyrophosphates: metabolism and signaling. Cell Mol Life Sci 2006;63:552-64.
5. Onnebo SM, Saiardi A. Inositol pyrophosphates get the vip1 treatment. Cell 2007;129:647-9. (Pubitemid 46802384)
6. Burton A, Hu X, Saiardi A. Are inositol pyrophosphates signalling molecules? Cell Physiol 2009;220:8-15.
7. Shears S. Diphosphoinositol polyphosphates: metabolic messengers? Mol Pharmacol 2009;76:236-52.
8. Kersting MC, Boyette M, Massey JH, Ryals PE. Identification of the inositol isomers present in tetrahymena. J Eukaryot Microbiol 2003;50:164-8. (Pubitemid 36720267)
9. Cosgrove DJ. The isolation of myoinositol pentaphosphates from hydrolysates of phytic acid. Biochem J 1963;89:172-5.
10. Raboy V, Gerbasi P. Genetics of myo-inositol phosphate synthesis and accumulation. Subcell Biochem 1996;26:257-85.
11. Putney JW Jr. Formation and actions of calcium-mobilizing messenger, inositol 1, 4, 5-trisphosphate. Am J Physiol 1987:252:G149-57.
12. Samanta S, Dalal B, Biswas S, Biswas BB. Myoinositol trisphosphatephytase complex as an elicitor in calcium mobilization in plants. Biochem Biophysical Res Commun 1993;191:427-34. (Pubitemid 23222653)
13. Dasgupta S, Dasgupta D, Sen M, Biswas S, Biswas BB. Interaction of myoinositoltrisphosphate-phytase complex with the receptor for intercellular Ca2+ mobilization in plants. Biochem 1996;35:4994-5001.
14. Goren MB, Dhariwal KR, Jenkins ID. Concerning hydrolysis of mycolate esters, of phthiocerol dimycocerosates and of related mycobacterial lipids: an anecdotal account. J Chromatogr 1988;440:487-98.
15. Belisle JT, Brandt ME, Radolf JD, Norgard MV. Fatty acids of treponema pallidum and borrelia burgdorferi lipoproteins. J Bacteriol 1994;176:2151-7. (Pubitemid 24118160)
16. Elsbach P, Weiss J. Phagocytosis of bacteria and phospholipid degradation. Biochim Biophys Acta 1988;947:29-52. (Pubitemid 18062312)
17. Kozloff LM, Turner MA, Arellano F, Lute M. Phosphatidylinositol, a phospholipid of ice-nucleating bacteria. J Bacteriol 1991;173:2053-60.
18. Salman M, Lonsdale JT, Besra GS, Brennan PJ. Phosphatidylinositol synthesis in mycobacteria. Biochim Biophys Acta 1999;1436:437-50. (Pubitemid 29242924)
19. Fahey RC. Novel thiols of prokaryotes. Annu Rev Microbiol 2001;55:333-56. (Pubitemid 32978109)
20. Reddy NR, Sathe SK, Salunkhe DK. Phytates in legumes and cereals. Adv Food Res 1982;28:1-92.
21. Walsh D, Grantham J, Zhu XO, et al. The role of heat shock proteins in mammalian differentiation and development. Environ Med 1999;43:79-87.
22. Pruitt RN, Chagot B, Cover M, Chazin WJ, Spiller B, Lacy DB. Structure-function analysis of inositol hexakisphosphate-induced autoprocessing in Clostridium difficile toxin A. J Biol Chem 2009;284:21934-40.
23. Prochazkova K, Shuvalova LA, Minasov G, Voburka Z, Anderson WF, Satchell KJ. Structural and molecular mechanism for autoprocessing of MARTX Toxin of Vibrio cholerae at multiple sites. J Biol Chem 2009;284:26557-68.
24. Steiner S, Smith S, Waechter CJ, Lester RL. Isolation and partial characterization of a major inositol-containing lipid in baker's yeast, mannosyl-diinositol, diphosphoryl-ceramide. Proc Natl Acad Sci U S A 1969;64:1042-8.
25. Uno I, Fukami K, Kato H, Takenawa T, Ishikawa T. Essential role for phosphatidylinositol 4, 5-bisphosphate in yeast cell proliferation. Nature 1988;333:188-90.
26. Robinson KS, Wheals AE, Rose AH, Dickinson JR. Unusual inositol triphosphate metabolism in yeast. Microbiology 1996;142(Pt 6):1333-4.
27. Silverman-Gavrila LB, Lew RR. An IP3-activated Ca2+ channel regulates fungal tip growth. J Cell Sci 2002;115:5013-25. (Pubitemid 36054651)
28. Tisi R, Belotti F, Wera S, Winderickx J, Thevelein JM, Martegani E. Evidence for inositol triphosphate as a second messenger for glucose-induced calcium signalling in budding yeast. Curr Genet 2004;45:83-9. (Pubitemid 38292229)
29. Nishizawa M, Komai T, Katou Y, Shirahige K, Ito T, Toh EA. Nutrient-regulated antisense and intragenic RNAs modulate a signal transduction pathway in yeast. PLoS Biol 2008;6:2817-30.
30. Lemtiri-Chlieh F, MacRobbie EA, Webb AA, et al. Inositol hexakisphosphate mobilizes an endomembrane store of calcium in guard cells. Proc Natl Acad Sci U S A 2003;100:10091-5. (Pubitemid 37087072)
31. Guilfoyle TJ, Hagen G. Auxin response factors. Curr Opin Plant Biol 2007;10:453-60. (Pubitemid 47505406)
32. Bohn L, Meyer AS, Rasmussen SK. Phytate: impact on environment and human nutrition. A challenge for molecular breeding. J Zhejiang Univ Sci B 2008;9:165-91. (Pubitemid 351447794)
33. Greiner R, Farouk AE, Carlsson NG, Konietzny U. myo-inositol phosphate isomers generated by the action of a phytase from a malaysian waste-water bacterium. Protein J 2007;26:577-84. (Pubitemid 350064253)
34. Doria. Phytic acid prevents oxidative stress in seeds: evidence from a maize (Zea mays L.) low phytic acid mutant. J Exp Bot 2009;60:967-78.
35. Murgia I, Arosio P, Tarantino D, Soave C. Biofortification for combating 'hidden hunger' for iron. Trends Plant Sci 2001;17:47-55.
36. Woodward AW, Bartel B. Auxin: regulation, action, and interaction. Ann Bot 2005;95:707-35. (Pubitemid 41238659)
37. Tan X, Zheng N. Hormone signaling through protein destruction: a lesson from plants. Am J Physiol Endocrinol Metab 2009:296:E223-7.
38. Shamsuddin AM. Metabolism and cellular functions of IP6: a review. Anticancer Res 1999;19:3733-6.
39. Sasakawa N, Sharif M, Hanley MR. Metabolism and biological activities of inositol pentakisphosphate and inositol hexakisphosphate. Biochem Pharmacol 1995;50:137-46.
40. Berridge MJ, Irvine RF. Inositol phosphates and cell signalling. Nature 1989;341:197-205. (Pubitemid 19231718)
41. Menniti FS, Oliver KG, Putney JW Jr, Shears SB. Inositol phosphates and cell signaling: new views of InsP5 and InsP6. Trends Biochem Sci 1993;18:53-6. (Pubitemid 23145112)
42. Vallejo M, Jackson T, Lightman S, Hanley MR. Occurrence and extracellular actions of inositol pentakis-and hexakisphosphate in mammalian brain. Nature 1987;330:656-8. (Pubitemid 18005580)
43. Hanley MR, Jackson TR, Vallejo M, et al. Neural function: metabolism and actions of inositol metabolites in mammalian brain. Philos Trans R Soc Lond B Biol Sci 1988;320:381-98.
44. Wilson HC, Bielinska M, Nicholas P, Majerus PW, Wilson DB. Neural tube defects in mice with reduced levels of inositol 1, 3, 4, - trisphosphate 5/6-kinase. Proc Amer Assoc Cancer Res 2009.
45. Rowley KG, Gundlach AL, Cincotta M, Louis WJ. Inositol hexakisphosphate binding sites in rat heart and brain. Br J Pharmacol 1996;118:1615-20. (Pubitemid 26252652)
46. O'Rourke F, Matthews E, Feinstein MB. Isolation of InsP4 and InsP6 binding proteins from human platelets: InsP4 promotes Ca2+ efflux from inside-out plasma membrane vesicles containing 104 kDa GAP1IP4BP protein. Biochem J 1996;315:1027-34.
47. Kitchen E, Condliffe AM, Rossi AG, Haslett C, Chilvers ER. Characterization of inositol hexakisphosphate (InsP6)-mediated priming in human neutrophils: lack of extracellular [3H]-InsP6 receptors. Br J Pharmacol 1996;117:979-85. (Pubitemid 26075977)
48. Eggleton P, Penhallow J, Crawford N. Priming action of inositol hexakisphosphate (InsP6) on the stimulated respiratory burst in human neutrophils. Biochim Biophys Acta 1991;1094:309-16.
49. Eggleton P. Effect of IP6 on human neutrophil cytokine production and cell morphology. Anticancer Res 1999;19:3711-5.
50. Ji H, Sandberg K, Baukal AJ, Catt KJ. Metabolism of inositol pentakisphosphate to inositol hexakisphosphate in Xenopus laevis oocytes. J Biol Chem 1989;264:20185-8. (Pubitemid 20009193)
51. Guse AH, Greiner E, Emmrich F, Brand K. Mass changes of inositol 1, 3, 4, 5, 6-pentakisphosphate and inositol hexakisphosphate during cell cycle progression in rat thymocytes. J Biol Chem 1993;268:7129-33. (Pubitemid 23105601)
52. Berridge MJ. Inositol trisphosphate and calcium signaling. Ann N Y Acad Sci 1995;766:31-43. (Pubitemid 26169079)
53. Taylor CW, Genazzani AA, Morris SA. Expression of inositol trisphosphate receptors. Cell Calcium 1999;26:237-51. (Pubitemid 30037825)
54. Roderick HL, Bootman MD. Bi-directional signalling from the InsP3 receptor: regulation by calcium and accessory factors. Biochem Soc Transac 2003;31:950-3. (Pubitemid 37305024)
55. Ho MW, Yang X, Carew MA, et al. Regulation of Ins (3, 4, 5, 6) P (4) signaling by a reversible kinase/phosphatase. Curr Biol 2002;12:477-82. (Pubitemid 34248894)
56. Nicoletti F, Bruno V, Fiore L, Cavallaro S, Canonico PL. Inositolhexakisphosphate (phytic acid) enhances Ca2+ influx and D-[3H]aspartate release in cultured cerebellar neurons. J Neurochem 1989;53:1026-30. (Pubitemid 19238464)
57. Sortino MA, Nicoletti F, Canonico PL. Inositol hexakisphosphate stimulates 45Ca2+ uptake in anterior pituitary cells in culture. Eur J Pharmacol 1990;189:115-8. (Pubitemid 20253005)
58. Copani A, Bruno V, Cavallaro S, et al. Receptors for inositol hexakisphosphate in neurons and anterior pituitary cells. Pharmacol Res 1990;22 Suppl 1:83-4. (Pubitemid 20375331)
59. Nicoletti F, Bruno V, Cavallaro S, Copani A, Sortino MA, Canonico PL. Specific binding sites for inositolhexakisphosphate in brain and anterior pituitary. Mol Pharmacol 1990;37:689-93. (Pubitemid 20171504)
60. Theibert AB, Estevez VA, Ferris CD, et al. Inositol 1, 3, 4, 5-tetrakisphosphate and inositol hexakisphosphate receptor proteins: isolation and characterization from rat brain. Proc Natl Acad Sci U S A 1991;88:3165-9. (Pubitemid 21916580)
61. Huisamen B, Lochner A. Inositolpolyphosphates and their binding proteins-a short review. Mol Cell Biochem 1996;157:229-32. (Pubitemid 26142457)
62. Shamsuddin AM, Baten A, Lalwani ND. Effects of inositol hexaphosphate on growth and differentiation in K-562 erythroleukemia cell line. Cancer Lett 1992;64:195-202.
63. Poyner DR, Cooke F, Hanley MR, Reynolds DJ, Hawkins PT. Characterization of metal ion-induced [3H]inositol hexakisphosphate binding to rat cerebellar membranes. J Biol Chem 1993;268:1032-8. (Pubitemid 23019738)
64. Palczewski K, Pulvermuller A, Buczylko J, Gutmann C, Hofmann KP. Binding of inositol phosphates to arrestin. FEBS Lett 1991;295:195-9.
65. Coppolino C. Hexa-citrated phytate and process of preparation thereof. U. S. Patent No 7, 009, 067 2006.
66. Coppolino C. Shamsuddin A. Novel phytic citrate compounds and process for preparing the same. U. S. Patent No 7, 517, 868, 2009.
67. Graf E, Eaton JW. Antioxidant functions of phytic acid. Free Radic Biol Med 1990;8:61-9.
68. Muraoka S, Miura T. Inhibition of xanthine oxidase by phytic acid and its antioxidative action. Life Sci 2004;74:1691-700.
69. Kolappaswamy K, Williams KA, Benazzi C, et al. Effect of inositol hexaphosphate on the development of UVB-induced skin tumors in SKH1 hairless mice. Comp Med 2009;59:147-52.
70. Rao PS, Liu XK, Das DK, Weinstein GS, Tyras DH. Protection of ischemic heart from reperfusion injury by myo-inositol hexaphosphate, a natural antioxidant. Ann Thorac Surg 1991;52:908-12.
71. Kamp DW, Israbian VA, Yeldandi AV, Panos RJ, Graceffa P, Weitzman SA. Phytic acid, an iron chelator, attenuates pulmonary inflammation and fibrosis in rats after intratracheal instillation of asbestos. Toxicol Pathol 1995;23:689-95. (Pubitemid 26021843)
72. Sudheer Kumar M, Sridhar Reddy B, Kiran Babu S, Bhilegaonkar PM, Shirwaikar A, Unnikrishnan MK. Antiinflammatory and antiulcer activities of phytic acid in rats. Indian J Exp Biol 2004;42:179-85. (Pubitemid 38192940)
73. Nelson RL, Yoo SJ, Tanure JC, Andrianopoulos G, Misumi A. The effect of iron on experimental colorectal carcinogenesis. Anticancer Res 1989;9:1477-82. (Pubitemid 20082116)
74. Singh A, Singh SP, Bamezai R. Modulatory influence of arecoline on the phytic acid-altered hepatic biotransformation system enzymes, sulfhydryl content and lipid peroxidation in a murine system. Cancer Lett 1997;117:1-6. (Pubitemid 27322907)
75. Porres JM, Stahl CH, Cheng WH, et al. Dietary intrinsic phytate protects colon from lipid peroxidation in pigs with a moderately high dietary iron intake. Proc Soc Exp Biol Med 1999;221:80-6.
76. Nascimento NR, Lessa LM, Kerntopf MR, et al. Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide. Proc Natl Acad Sci U S A 2006;103:218-23. (Pubitemid 43076130)
77. Thompson LU, Zhang L. Phytic acid and minerals: effect on early markers of risk for mammary and colon carcinogenesis. Carcinogenesis 1991;12:2041-5.
78. Morton RK, Raison JK. A Complete intracellular unit for incorporation of amino-acid into storage protein utilizing adenosine triphosphate generated from phytate. Nature 1963;200:429-33.
79. Biswas S, Maity IB, Chakrabarti S, Biswas BB. Purification and characterization of myo-inositol hexaphosphate-adenosine diphosphate phosphotransferase from Phaseolus aureus. Arch Biochem Biophys 1978;185:557-66. (Pubitemid 8291119)
80. Josefsen L, Bohn L, Sorensen MB, Rasmussen SK. Characterization of a multifunctional inositol phosphate kinase from rice and barley belonging to the ATP-grasp superfamily. Gene 2007;397:114-25. (Pubitemid 46977138)
81. Phillippy BQ, Ullah AH, Ehrlich KC. Purification and some properties of inositol 1, 3, 4, 5, 6-Pentakisphosphate 2-kinase from immature soybean seeds. [erratum appears in J Biol Chem 1995 Mar. 31;270(13):7782]. J Biol Chem 1994;269:28393-9. (Pubitemid 24354583)
82. Efanov AM, Zaitsev SV, Berggren PO. Inositol hexakisphosphate stimulates non-Ca2+-mediated and primes Ca2+-mediated exocytosis of insulin by activation of protein kinase C. Proc Natl Acad Sci U S A 1997;94:4435-9.
83. Larsson O, Barker CJ, Sjoholm A, et al. Inhibition of phosphatases and increased Ca2+ channel activity by inositol hexakisphosphate. Sci 1997;278:471-4. (Pubitemid 27454432)
84. Ferry S, Matsuda M, Yoshida H, Hirata M. Inositol hexakisphosphate blocks tumor cell growth by activating apoptotic machinery as well as by inhibiting the Akt/NFkappaB-mediated cell survival pathway. [erratum appears in Carcinogenesis. 2003 Jan; 24(1):149]. Carcinogenesis 2002;23:2031-41. (Pubitemid 36109120)
85. Singh RP, Sharma G, Mallikarjuna GU, Dhanalakshmi S, Agarwal C, Agarwal R. In vivo suppression of hormone-refractory prostate cancer growth by inositol hexaphosphate: induction of insulin-like growth factor binding protein-3 and inhibition of vascular endothelial growth factor. Clini Cancer Res 2004;10:244-50. (Pubitemid 38114186)
86. Cole KE, Smith M, Xu J-F, Vucenik I, Shamsuddin, A. M. Modulation of the intracellular calcium signal in human colon cancer cells by the novel antineoplastic agent inositol Hexaphosphate. Anticancer Res; 17:4070-1, 1997.
87. Lu YJ, He Y, Sui SF. Inositol hexakisphosphate (InsP6) can weaken the Ca (2+)-dependent membrane binding of C2AB domain of synaptotagmin I. FEBS Letters 2002;527:22-6. (Pubitemid 35253832)
88. Grases F, Costa-Bauza A, Prieto RM. A potential role for crystallization inhibitors in treatment of alzheimer's disease. Med Hypotheses 2009;74:118-9.
89. Hoy M, Efanov AM, Bertorello AM, et al. Inositol hexakisphosphate promotes dynamin I-mediated endocytosis. Proc Natl Acad Sci U S A 2002;99:6773-7. (Pubitemid 34526207)
90. Lamaze C, Baba T, Redelmeier TE, Schmid SL. Recruitment of epidermal growth factor and transferrin receptors into coated pits in vitro: differing biochemical requirements. Mol Biol Cell 1993;4:715-27. (Pubitemid 23227157)
91. Zi X, Singh RP, Agarwal R. Impairment of erbB1 receptor and fluid-phase endocytosis and associated mitogenic signaling by inositol hexaphosphate in human prostate carcinoma DU145 cells. Carcinogenesis 2000;21:2225-35. (Pubitemid 32049229)
92. Voglmaier SM, Keen JH, Murphy JE, et al. Inositol hexakisphosphate receptor identified as the clathrin assembly protein AP-2. Biochem Biophys Res Commun 1992;187:158-63.
93. Morrison RS, Shi E, Kan M, et al. Inositolhexakisphosphate (InsP6): an antagonist of fibroblast growth factor receptor binding and activity. In Vitro Cell Dev Biol Ani 1994;30 A: 783-89. (Pubitemid 24376743)
94. Kar S, Quirion R, Parent A. An interaction between inositol hexakisphosphate (IP6) and insulin-like growth factor II receptor binding sites in the rat brain. Neuroreport 1994;5:625-28. (Pubitemid 24091355)
95. Couchman JR, Vogt S, Lim ST, et al. Regulation of inositol phospholipid binding and signaling through syndecan-4. J Biol Chem 2002;277:49296-303. (Pubitemid 36014359)
96. Tantivejkul K, Vucenik I, Shamsuddin AM. Inositol hexaphosphate (IP6) inhibits key events of cancer metastasis: I. In vitro studies of adhesion, migration and invasion of MDA-MB 231 human breast cancer cells. Anticancer Res 2003;23:3671-79. (Pubitemid 37474310)
97. Tantivejkul K, Vucenik I, Shamsuddin AM. Inositol hexaphosphate (IP6) inhibits key events of cancer metastasis: II. Effects on integrins and focal adhesions. Anticancer Res 2003;23:3681-9. (Pubitemid 37474311)
98. Vucenik I, Shamsuddin AM. Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic. J Nutr 2003;133:3778S-84S. (Pubitemid 37392600)
99. Shamsuddin AM, Vucenik I, Cole KE. IP6: a novel anti-cancer agent. Life Sci 1997;61:343-54.
100. Shamsuddin AM, Ullah A, Chakravarthy AK. Inositol and inositol hexaphosphate suppress cell proliferation and tumor formation in CD-1 mice. Carcinogenesis 1989;10:1461-3. (Pubitemid 19197465)
101. Vucenik I, Ramakrishna G, Tantivejkul K, Anderson LM, Ramljak D. Inositol hexaphosphate (IP6) blocks proliferation of human breast cancer cells through a PKCdelta-dependent increase in p27Kip1 and decrease in retinoblastoma protein (pRb) phosphorylation. Breast Cancer Res Treat 2005;91:35-45. (Pubitemid 40684937)
102. Yang GY, Shamsuddin AM. IP6-induced growth inhibition and differentiation of HT-29 human colon cancer cells: involvement of intracellular inositol phosphates. Anticancer Res 1995;15:2479-87. (Pubitemid 26095050)
103. Vucenik S. Antiproliferative effects inositol hexaphosphate (IP6) in breast cancer cells is mediated by increase in p27 and decrease in Rb protein phosphorylation. Proc Amer Assoc Cancer Res 2000.
104. El-Sherbiny YM, Cox MC, Ismail ZA, Shamsuddin AM, Vucenik I. G0/G1 arrest and S phase inhibition of human cancer cell lines by inositol hexaphosphate (IP6). Anticancer Res 2001;21:2393-403. (Pubitemid 33054401)
105. Barker CJ, Wright J, Kirk CJ, Michell RH. Inositol 1, 2, 3-trisphosphate is a product of InsP6 dephosphorylation in WRK-1 rat mammary epithelial cells and exhibits transient concentration changes during the cell cycle. Biochem Soc Transactions 1995;23:169S.
106. Singh RP, Agarwal C, Agarwal R. Inositol hexaphosphate inhibits growth, and induces G1 arrest and apoptotic death of prostate carcinoma DU145 cells: modulation of CDKI-CDK-cyclin and pRb-related protein-E2F complexes. Carcinogenesis 2003;24:555-63. (Pubitemid 36432653)
107. Deliliers GL, Servida F, Fracchiolla NS, et al. Effect of inositol hexaphosphate (IP (6)) on human normal and leukaemic haematopoietic cells. Br J Haematol 2002;117:577-87. (Pubitemid 34539231)
108. Sakamoto K, Venkatraman G, Shamsuddin AM. Growth inhibition and differentiation of HT-29 cells in vitro by inositol hexaphosphate (phytic acid). Carcinogenesis 1993;14:1815-19. (Pubitemid 23290893)
109. Shamsuddin AM, Yang GY. Inositol hexaphosphate inhibits growth and induces differentiation of PC-3 human prostate cancer cells. Carcinogenesis 1995;16:1975-9.
110. Shamsuddin AM, Yang GY, Vucenik I. Novel anti-cancer functions of IP6: growth inhibition and differentiation of human mammary cancer cell lines in vitro. Anticancer Res 1996;16:3287-92. (Pubitemid 27085072)
111. Vucenik I, Kalebic T, Tantivejkul K, Shamsuddin AM. Novel anticancer function of inositol hexaphosphate: inhibition of human rhabdomyosarcoma in vitro and in vivo. Anticancer Res 1998;18:1377-84. (Pubitemid 28342534)
112. Bertagnolo V, Neri LM, Marchisio M, Mischiati C, Capitani S. Phosphoinositide 3-kinase activity is essential for all-trans-retinoic acid-induced granulocytic differentiation of HL-60 cells. Cancer Res 1999;59:542-6. (Pubitemid 29076047)
113. Pittet D, Schlegel W, Lew DP, Monod A, Mayr GW. Mass changes in inositol tetrakis-and pentakisphosphate isomers induced by chemotactic peptide stimulation in HL-60 cells. J Biol Chem 1989;264:18489-93. (Pubitemid 19277594)
114. Nagata E, Luo HR, Saiardi A, Bae BI, Suzuki N, Snyder SH. Inositol hexakisphosphate kinase-2, a physiologic mediator of cell death. J Biol Chem 2005;280:1634-40.
115. Karmakar S, Banik NL, Ray SK. Molecular mechanism of inositol hexaphosphate-mediated apoptosis in human malignant glioblastoma T98G cells. Neurochem Res 2007;32:2094-102. (Pubitemid 350059853)
116. Diallo JS, Betton B, Parent N, et al. Enhanced killing of androgenindependent prostate cancer cells using inositol hexakisphosphate in combination with proteasome inhibitors. Br J Cancer 2008;99:1613-22.
117. Singh J, Gupta KP. Inositol hexaphosphate induces apoptosis by coordinative modulation of p53, Bcl-2 and sequential activation of caspases in 7, 12 dimethylbenz (a) anthracene exposed mouse epidermis. J Environ Pathol Toxicol Oncol 2008;27:209-17.
118. Xu Q, Kanthasamy G, Reddy MB. Phytic acid protects against 6-OHDA and iron induced apoptosis in cell culture model of Parkinson's disease. Parkinsons Dis 2011;2011:431068.
119. Jagadeesh S, Banerjee PP. Inositol hexaphosphate represses telomerase activity and translocates TERT from the nucleus in mouse and human prostate cancer cells via the deactivation of Akt and PKCalpha. Biochem Biophysic Res Commun 2006;349:1361-7. (Pubitemid 44416407)
120. Solyakov L, Cain K, Tracey BM, et al. Regulation of casein kinase-2 (CK2) activity by inositol phosphates. J Biol Chem 2004;279:43403-10. (Pubitemid 39390639)
121. Huang C, Ma WY, Hecht SS, Dong Z. Inositol hexaphosphate inhibits cell transformation and activator protein 1 activation by targeting phosphatidylinositol-3' kinase.[erratum appears in Cancer Res 1997 Nov. 15; 57(22):5198]. Cancer Res 1997;57:2873-8. (Pubitemid 27315031)
122. Vucenik I, Ramakrishna G, Tantivejkul K, Anderson L, Ramljak D. Inositol hexaphosphate (IP6) differentially modulates the expression of PKĆ in MCF-7 and MDA-MB 231 cells. Proc Amer Assoc Cancer Res 1999.
123. Vucenik I, Ramljak D. The contradictory role of PKCdelta in cellular signaling. Breast Cancer Res Treat 2006;97:1-2.
124. Nickel KP, Belury MA. Inositol hexaphosphate reduces 12- Otetradecanoylphorbol-13-acetate-induced ornithine decarboxylase independent of protein kinase C isoform expression in keratinocytes. Cancer Lett 1999;140:105-11. (Pubitemid 29251320)
125. Chen N, Ma WY, Dong Z. Inositol hexaphosphate inhibits ultraviolet B-induced signal transduction. Mol Carcinog 2001;31:139-44. (Pubitemid 32744533)
126. Hoy M, Berggren PO, Gromada J. Involvement of protein kinase C-epsilon in inositol hexakisphosphate-induced exocytosis in mouse pancreatic beta-cells. J Biol Chem 2003;278:35168-71.
127. Cocco L, Martelli AM, Barnabei O, Manzoli FA. Nuclear inositol lipid signaling. Adv Enzyme Regul 2001;41:361-84.
128. Cocco L, Manzoli L, Barnabei O, Martelli AM. Significance of subnuclear localization of key players of inositol lipid cycle. Adv Enzyme Regul 2004;44:51-60. (Pubitemid 39568164)
129. Cocco L, Gilmour RS, Ognibene A, Letcher AJ, Manzoli FA, Irvine RF. Synthesis of polyphosphoinositides in nuclei of Friend cells. Evidence for polyphosphoinositide metabolism inside the nucleus which changes with cell differentiation. Biochem J 1987;248:765-70.
130. Cocco L, Martelli AM, Vitale M, Falconi M, Barnabei O, Stewart Gilmour R, Manzoli FA. Inositides in the nucleus: regulation of nuclear PI-PLCbeta1. Adv Enzyme Regul 2002;42:181-93. (Pubitemid 35033538)
131. York JD, Odom AR, Murphy R, Ives EB, Wente SR. A phospholipase C-dependent inositol polyphosphate kinase pathway required for efficient messenger RNA export. Sci 1999;285:96-100. (Pubitemid 29307573)
132. Alcazar-Roman AR, Tran EJ, Guo S, Wente SR. Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA export. Nature Cell Biol 2006;8:711-16.
133. Weirich CS, Erzberger JP, Flick JS, Berger JM, Thorner J, Weis K. Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export. Nature Cell Biol 2006;8:668-76.
134. Cole CN, Scarcelli JJ. Transport of messenger RNA from the nucleus to the cytoplasm. Curr Opinion in Cell Biol 2006;18:299-306.
135. Gross T, Siepmann A, Sturm D, et al. The DEAD-box RNA helicase Dbp5 functions in translation termination. Sci 2007;315:646-9. (Pubitemid 46214708)
136. Ongusaha PP, Hughes PJ, Davey J, Michell RH. Inositol hexakisphosphate in Schizosaccharomyces pombe: synthesis from Ins (1, 4, 5) P3 and osmotic regulation. Biochem J 1998;335:671-9. (Pubitemid 28515423)
137. Odom AR, Stahlberg A, Wente SR, York JD. A role for nuclear inositol 1, 4, 5-trisphosphate kinase in transcriptional control. Sci 2000;287:2026-9. (Pubitemid 30158681)
138. Macbeth MR, Schubert HL, Vandemark AP, Lingam AT, Hill CP, Bass BL. Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing. Sci 2005;309:1534-9. (Pubitemid 41266474)
139. Zhang Z, Carmichael GG. The fate of dsRNA in the nucleus: a p54 (nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell 2001;106:465-75. (Pubitemid 32786990)
140. Shen X, Xiao H, Ranallo R, Wu WH, Wu C. Modulation of ATPdependent chromatin-remodeling complexes by inositol polyphosphates. Sci 2003;299:112-4. (Pubitemid 36042414)
141. Steger DJ, Haswell ES, Miller AL, Wente SR, O'Shea EK. Regulation of chromatin remodeling by inositol polyphosphates. Sci 2003;299:114-6. (Pubitemid 36042415)
142. Hanakahi LA, Bartlet-Jones M, Chappell C, Pappin D, West SC. Binding of inositol phosphate to DNA-PK and stimulation of double-strand break repair. Cell 2000;102:721-9.
143. Ma Y, Lieber MR. Binding of inositol hexakisphosphate (IP6) to Ku but not to DNA-PKcs. J Biol Chem 2002;277:10756-9. (Pubitemid 34952827)
144. Byrum J, Jordan S, Safrany ST, Rodgers W. Visualization of inositol phosphate-dependent mobility of Ku: depletion of the DNA-PK cofactor InsP6 inhibits Ku mobility. Nucleic Acids Res 2004;32:2776-84. (Pubitemid 38885949)
145. Cheung JC, Salerno B, Hanakahi LA. Evidence for an inositol hexakisphosphate-dependent role for Ku in mammalian nonhomologous end joining that is independent of its role in the DNA-dependent protein kinase. Nucleic Acids Res 2008;36:5713-26.
146. Agarwal C, Dhanalakshmi S, Singh RP, Agarwal R. Inositol hexaphosphate inhibits constitutive activation of NF-kappa B in androgen-independent human prostate carcinoma DU145 cells. Anticancer Res 2003;23:3855-61. (Pubitemid 37474334)
147. Kapral M, Parfiniewicz B, Strzǎka-Mrozik B, Zachacz A, Weglarz L. Evaluation of the expression of transcriptional factor NF-kappaB induced by phytic acid in colon cancer cells. Acta Pol Pharm 2008:697-702.
148. Janus SC, Weurtz B, Ondrey FG. Inositol hexaphosphate and paclitaxel: symbiotic treatment of oral cavity squamous cell carcinoma. Laryngoscope 2007;117:1381-8. (Pubitemid 47356839)
149. Baten A, Ullah A, Tomazic VJ, Shamsuddin AM. Inositolphosphateinduced enhancement of natural killer cell activity correlates with tumor suppression. Carcinogenesis 1989;10:1595-8. (Pubitemid 19222255)
150. Zhang Z, Song Y, Wang XL. Inositol hexaphosphate-induced enhancement of natural killer cell activity correlates with suppression of colon carcinogenesis in rats. World Journal of Gastroenterology 2005;11:5044-6. (Pubitemid 41227209)
151. Cholewa K, Parfiniewicz B, Bednarek I, Swiatkowska L, Jezienicka E, Kierot J, Weglarz L. The influence of phytic acid on TNF-alpha and its receptors genes' expression in colon cancer Caco-2 cells. Acta Pol Pharmaceutica 2008;65:75-9. (Pubitemid 351578431)
152. Shamsuddin A. Anti-cancer function of phytic acid. Int J Food Sci Technol 2002;37:760-82.
153. Shamsuddin AM, Elsayed AM, Ullah A. Suppression of large intestinal cancer in F344 rats by inositol hexaphosphate. Carcinogenesis 1988;9:577-80.
154. Norazalina NM, Hairuszah I, Norashareena MS. Anticarcinogenic efficacy of phytic acid extracted from rice bran on azoxymethaneinduced colon carcinogenesis in rats. Exp Toxicol Pathol 2010;62:259-68.
155. Ullah A, Shamsuddin AM. Dose-dependent inhibition of large intestinal cancer by inositol hexaphosphate in F344 rats. Carcinogenesis 1990;11:2219-22.
156. Shivapurkar N, Tang ZC, Frost A, Alabaster O. A rapid dual organ rat carcinogenesis bioassay for evaluating the chemoprevention of breast and colon cancer. Cancer Lett 1996;100:169-79. (Pubitemid 26053942)
157. Pretlow TP, O'Riordan MA, Somich GA, Amini SB, Pretlow TG. Aberrant crypts correlate with tumor incidence in F344 rats treated with azoxymethane and phytate. Carcinogenesis 1992;13:1509-12.
158. Challa A, Rao DR, Reddy BS. Interactive suppression of aberrant crypt foci induced by azoxymethane in rat colon by phytic acid and green tea. Carcinogenesis 1997;18:2023-6. (Pubitemid 28132391)
159. Jenab M, Thompson LU. Phytic acid in wheat bran affects colon morphology, cell differentiation and apoptosis. Carcinogenesis 2000;21:1547-52. (Pubitemid 30603979)
160. Jariwalla RJ, Sabin R, Lawson S, et al. Effects of dietary phytic acid (phytate) on the incidence and growth rate of tumors promoted in Fisher rats by a magnesium supplement. Nutri Res 1988:813-27.
161. Ishikawa T, Nakatsuru Y, Zarkovic M, Shamsuddin AM. Inhibition of skin cancer by IP6 in vivo: initiation-promotion model. Anticancer Res 1999;19:3749-52.
162. Gupta KP, Singh J, Bharathi R. Suppression of DMBA-induced mouse skin tumor development by inositol hexaphosphate and its mode of action. Nutri Cancer 2003;46:66-72. (Pubitemid 37163293)
163. Lee HJ, Lee SA, Choi H. Dietary administration of inositol and/or inositol-6-phosphate prevents chemically-induced rat hepatocarcinogenesis. Asian Pacific J Cancer Prev: Apjcp 2005;6:41-7.
164. Hirose M, Ozaki K, Takaba K, Fukushima S, Shirai T, Ito N. Modifying effects of the naturally occurring antioxidants gammaoryzanol, phytic acid, tannic acid and n-tritriacontane-16, 18-dione in a rat wide-spectrum organ carcinogenesis model. Carcinogenesis 1991;12:1917-21.
165. Raina K, Rajamanickam S, Singh RP, Agarwal R. Chemopreventive efficacy of inositol hexaphosphate against prostate tumor growth and progression in TRAMP mice. Clin Cancer Res 2008;14:3177-84.
166. Kolappaswamy K, Williams KA, Benazzi C, et al. Effect of inositol hexaphosphate on the development of UVB-induced skin tumors in SKH1 hairless mice. Comp Med 2009;59:147-52.
167. Vucenik I, Sakamoto K, Bansal M, Shamsuddin AM. Inhibition of rat mammary carcinogenesis by inositol hexaphosphate (phytic acid). A pilot study. Cancer Lett 1993;75:95-102. (Pubitemid 24014532)
168. Vucenik I, Yang GY, Shamsuddin AM. Inositol hexaphosphate and inositol inhibit DMBA-induced rat mammary cancer. Carcinogenesis 1995;16:1055-8.
169. Estensen RD, Wattenberg LW. Studies of chemopreventive effects of myo-inositol on benzo[a]pyrene-induced neoplasia of the lung and forestomach of female A/J mice. Carcinogenesis 1993;14:1975-7. (Pubitemid 23290920)
170. Wattenberg LW. Chemoprevention of pulmonary carcinogenesis by myo-inositol. Anticancer Res 1999;19:3659-61.
171. Druzijanic N, Juricic J, Perko Z, Kraljevic D. IP6 + Inositol as adjuvant to chemotherapy of colon cancer: Our clinical experience. Anticancer Res 2004:3474.
172. Sun AS, Yeh HC, Wang LH, et al. Pilot study of a specific dietary supplement in tumor-bearing mice and in stage IIIB and IV nonsmall cell lung cancer patients. Nutri Cancer 2001;39:85-95. (Pubitemid 32880953)
173. Druzijanic N, Juricic J, Perko Z, Kraljevic D. IP-6 and Inositol: adjuvant to chemotherapy of colon cancer. A pilot clinical trial. Rev Oncol 2002;4:171.
174. Vucenik I, Shamsuddin A. Inositol hexaphosphate (IP6) reduces risk for cancer and cardiovascular diseases. Period Biol 1997:25-30. (Pubitemid 27292381)
175. Druzijanic N, Juricic J, Perko Z, Kraljevic D. IP-6 & Inositol: adjuvant to chemotherapy of colon cancer. A pilot clinical trial. Rev Oncol 4(Suppl 1) 2002;170.
176. Vucenik I, Tantivejkul K, Zhang ZS, Cole KE, Saied I, Shamsuddin AM. IP6 in treatment of liver cancer. I. IP6 inhibits growth and reverses transformed phenotype in HepG2 human liver cancer cell line. Anticancer Res 1998;18:4083-90. (Pubitemid 29043616)
177. Vucenik I, Passaniti A, Vitolo MI, Tantivejkul K, Eggleton P, Shamsuddin AM. Anti-angiogenic activity of inositol hexaphosphate (IP6). Carcinogenesis 2004;25:2115-23. (Pubitemid 39534848)
178. Vucenik I, Shamsuddin AM. Protection against cancer by dietary IP6 and inositol. Nutri Cancer 2006;55:109-25. (Pubitemid 44719624)
179. Howell A. The endocrine prevention of breast cancer. Best Practice & Research Clini Endocrinol Metab 2008;22:615-23.
180. Schiff R, Reddy P, Ahotupa M et al. Oxidative stress and AP-1 activity in tamoxifen-resistant breast tumors in vivo. Journal of the National Cancer Inst 2000;92:1926-34. (Pubitemid 32036923)
181. De Graffenried LA, Chandrasekar B, Friedrichs WE, et al. NFkappa B inhibition markedly enhances sensitivity of resistant breast cancer tumor cells to tamoxifen. Ann Oncol 2004;15:885-90. (Pubitemid 39004343)
182. Carroll JS, Lynch DK, Swarbrick A, et al. p27 (Kip1) induces quiescence and growth factor insensitivity in tamoxifen-treated breast cancer cells. Cancer Res 2003;63:4322-6. (Pubitemid 36950997)
183. Donovan JC, Milic A, Slingerland JM. Constitutive MEK/MAPK activation leads to p27 (Kip1) deregulation and antiestrogen resistance in human breast cancer cells. J Biol Chem 2001;276:40888-95.
184. Gee JM, Robertson JF, Ellis IO, Nicholson RI. Phosphorylation of ERK1/2 mitogen-activated protein kinase is associated with poor response to anti-hormonal therapy and decreased patient survival in clinical breast cancer. Int J Cancer 2001;95:247-54. (Pubitemid 32592092)
185. Jordan NJ, Gee JM, Barrow D, Wakeling AE, Nicholson RI. Increased constitutive activity of PKB/Akt in tamoxifen resistant breast cancer MCF-7 cells. Breast Cancer Res Treat 2004;87:167-80. (Pubitemid 39237793)
186. De Graffenried LA, Friedrichs WE, Russell DH, Donzis EJ, Middleton AK, Silva JM, Roth RA, Hidalgo M. Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt Activity. Clin Cancer Res 2004;10:8059-67. (Pubitemid 39587547)
187. Roy S, Singh RP, Agarwal C, Siriwardana S, Sclafani R, Agarwal R. Downregulation of both p21/Cip1 and p27/Kip1 produces a more aggressive prostate cancer phenotype. Cell Cycle 2008;7:1828-35. (Pubitemid 351988749)
188. Roy S, Gu M, Ramasamy K, Singh RP, Agarwal C, Siriwardana S, Sclafani RA, Agarwal R. p21/Cip1 and p27/Kip1 Are essential molecular targets of inositol hexaphosphate for its antitumor efficacy against prostate cancer. Cancer Res 2009:1166-73.
189. Hattori Y, Shi, L, Ding, W, Koga, K. Novel irinotecan-loaded liposome using phytic acid with high therapeutic efficacy for colon tumors. J Cont release 2009;136:30-7.
190. Matejuk A, Shamsuddin A, M. IP6 in Cancer Therapy: Past, Present and Future. Curr Cancer Ther Rev 2010;6:1-12.
191. Grases F, March JG, Prieto RM, et al. Urinary phytate in calcium oxalate stone formers and healthy people-dietary effects on phytate excretion. Scand J Urol Nephrol 2000;34:162-4. (Pubitemid 32055263)
192. Grases F, Perello J, Prieto RM, Simonet BM, Torres JJ. Dietary myo-inositol hexaphosphate prevents dystrophic calcifications in soft tissues: a pilot study in Wistar rats. Life Sci 2004;75:11-9. (Pubitemid 38501761)
193. Jariwalla RJ, Sabin R, Lawson S, Herman ZS. Lowering of serum cholesterol and triglycerides and modulations by dietary phytate. J Appl Nutr 1990:18-28.
194. Vucenik I, Podczasy JJ, Shamsuddin AM. Antiplatelet activity of inositol hexaphosphate (IP6). Anticancer Res 1999;19:3689-93.
195. Jariwalla RJ. Inositol hexaphosphate (IP6) as an anti-neoplastic and lipid-lowering agent. Anticancer Research 1999;19:3699-702.
196. Schlemmer U, Frolich W, Prieto RM, Grases F. Phytate in foods and significance for humans: Food sources, intake, processing, bioavailability, protective role and analysis. Mol Nutr Food Res 2009;53 Suppl 2:S330-75.
197. Grases F, Simonet BM, Vucenik I, et al. Absorption and excretion of orally administered inositol hexaphosphate (IP (6) or phytate) in humans. Biofactors 2001;15:53-61. (Pubitemid 34014664)
198. Grases F, Simonet BM, Vucenik I, Perello J, Prieto RM, Shamsuddin AM. Effects of exogenous inositol hexakisphosphate (InsP (6)) on the levels of InsP (6) and of inositol trisphosphate (InsP (3)) in malignant cells, tissues and biological fluids. Life Sci 2002;71:1535-46. (Pubitemid 34804586)
199. 6 + Inositol: Nature's Medicine for the Millennium. Amazon.com. 2011 [http://www.amazon.com/IP6-Inositol-Medicine- Millenniumebook/dp/B004QOB71W/ref=sr-1-3?ie=UTF8&m=AG56TWVU5XWC2&s= digital-text&qid=1301896887&sr=1-3]