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Current Cancer Therapy Reviews

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ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

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Review Article

Oxidative Stress and Cellular Senescence: The Key Tumor-promoting Factors in Colon Cancer and Beneficial Effects of Polyphenols in Colon Cancer Prevention

Author(s): Meenu Bhatiya, Surajit Pathak and Antara Banerjee*

Volume 17, Issue 4, 2021

Published on: 14 July, 2021

Page: [292 - 303] Pages: 12

DOI: 10.2174/1573394717666210715165127

Price: $65

Abstract

Background: Colon cancer is the third leading cause of cancer-related deaths worldwide. Colon tumorigenesis is a sequential process called “Adenoma-carcinoma sequence”. The alimentary habits, obesity, heavy alcohol consumption, inflammatory bowel diseases, family history of colon cancer, oxidative stress, and cellular senescence are the major risk factor influencing colon cancer development. Senescence contributes to the aging process as well as the development and progression of colon cancer. However, the precise mechanism underlying the aging-related progress of colon cancer is yet to be answered. Recent studies proposed that the senescent cell secretes Senescence-Associated Secretory Phenotype (SASP) includes pro-inflammatory cytokines, interleukins, growth factors, and proteases actively involved in the creation of pro-tumorigenic microenvironment.

Objective: This review aims to provide an overview of ROS influence cellular senescence and colon cancer development as well as summarize the antioxidant and antiaging activity of natural flavonoids. Many of the studies had reported that pro-aging genes suppress cancer and various ‘markers’ are used to identify senescent cells in vitro and in vivo. The SASP of the cells may act as a link between senescence and cancer.

Conclusion: This review facilitates a better understanding and might contribute to diagnostic and prognostic systems as well as to find out the novel and targeted therapeutic approaches. Additionally, we focused on the potential role of natural flavonoids in colon cancer therapies and highlighting the flavonoid-based treatments as innovative immunomodulatory strategies to inhibit the growth of colon cancer.

Keywords: Colon cancer, aging, oxidative stress, flavonoid, reactive oxygen species, cellular senescence.

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[1]
Moazeni-Roodi A, Hashemi M. Association between miR-124-1 rs531564 polymorphism and risk of cancer: An updated meta-analysis of case-control studies. EXCLI J 2018; 17: 608-19.
[PMID: 30108465]
[2]
Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 2016; 66(4): 271-89.
[http://dx.doi.org/10.3322/caac.21349] [PMID: 27253694]
[3]
Giovannucci E. Diet, body weight, and colorectal cancer: A summary of the epidemiologic evidence. J Womens Health (Larchmt) 2003; 12(2): 173-82.
[http://dx.doi.org/10.1089/154099903321576574] [PMID: 12737716]
[4]
Tan BL, Norhaizan ME, Liew WP. Sulaiman, Rahman, H. Antioxidant and oxidative stress: a mutual interplay in age-related diseases. Front Pharmacol 2018; 16: 9-1162.
[5]
Banerjee A, Pathak S, Jothimani G, Roy S. Antiproliferative effects of combinational therapy of Lycopodium clavatum and quercetin in colon cancer cells. J Basic Clin Physiol Pharmacol 2020; 12: 31.
[6]
Skrzydlewska E, Stankiewicz A, Sulkowska M, Sulkowski S, Kasacka I. Antioxidant status and lipid peroxidation in colorectal cancer. J Toxicol Environ Health Sci A 2001; 64(3): 213-22.
[7]
Mantovani G, Macciò A, Madeddu C, et al. Quantitative evaluation of oxidative stress, chronic inflammatory indices and leptin in cancer patients: Correlation with stage and performance status. Int J Cancer 2002; 98(1): 84-91.
[http://dx.doi.org/10.1002/ijc.10143] [PMID: 11857390]
[8]
Hassanzade J, Molavi e vardanjani H, Farahmand M, Rajaiifard AR. Incidence and mortality rate of common gastrointestinal cancers in South of Iran, a population based study. Iran J Cancer Prev 2011; 4(4): 163-9.
[9]
Bhawna S. Consensus document for management of colorectal cancer. Retrieved 2014; 10: 2017.
[10]
Subramaniam R, Mizoguchi A, Mizoguchi E. Mechanistic roles of epithelial and immune cell signaling during the development of colitis-associated cancer. Cancer Res Front 2016; 2(1): 1-21.
[http://dx.doi.org/10.17980/2016.1] [PMID: 27110580]
[11]
Simon K. Colorectal cancer development and advances in screening. Clin Interv Aging 2016; 11: 967-76.
[http://dx.doi.org/10.2147/CIA.S109285] [PMID: 27486317]
[12]
Cheeseman KH, Slater TF. An introduction to free radical biochemistry. Br Med Bull 1993; 49(3): 481-93.
[http://dx.doi.org/10.1093/oxfordjournals.bmb.a072625] [PMID: 8221017]
[13]
Deka D, Scarpa M, Das A, Pathak S, Banerjee A. Current understanding of epigenetics driven therapeutic strategies in colorectal cancer management. Endocr Metab Immune Disord Drug Targets 2021; 21: 1-10.
[http://dx.doi.org/10.2174/1871530321666210219155544] [PMID: 33605866]
[14]
Banerjee A, Chabria Y, Kanna N R R, et al. Role of tumor specific niche in colon cancer progression and emerging therapies by targeting tumor microenvironment. Adv Exp Med Biol 2019; 2019: 1-16.
[http://dx.doi.org/10.1007/5584_2019_355] [PMID: 30969400]
[15]
Ebner DW, Kisiel JB. Stool-based tests for colorectal cancer screening: Performance benchmarks lead to high expected efficacy. Curr Gastroenterol Rep 2020; 22: 1-9.
[16]
Aruoma OI. Nutrition and health aspects of free radicals and antioxidants. Food Chem Toxicol 1994; 32(7): 671-83.
[PMID: 8045480]
[17]
Afanas’ev I. Reactive oxygen species signaling in cancer: Comparison with aging. Aging Dis 2011; 2(3): 219-30.
[PMID: 22396874]
[18]
Galadari S, Rahman A, Pallichankandy S, Thayyullathil F. Reactive oxygen species and cancer paradox: To promote or to suppress? Free Radic Biol Med 2017; 104: 144-64.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.01.004] [PMID: 28088622]
[19]
Dröge W. Free radicals in the physiological control of cell function. Physiol Rev 2002; 82(1): 47-95.
[http://dx.doi.org/10.1152/physrev.00018.2001] [PMID: 11773609]
[20]
Cui H, Kong Y, Zhang H. Oxidative stress, mitochondrial dysfunction, and aging. J Signal Transduct 2012; 2012: 646354.
[http://dx.doi.org/10.1155/2012/646354] [PMID: 21977319]
[21]
Di MS, Reed TT, Venditti P, Victor VM. Role of ROS and RNS sources in physiological and pathological conditions. Oxid Med Cell Longev 2016; 2016: 1245049.
[22]
Schröder M, Kaufman R. ER stress and the unfolded protein response. Mutat Res-Fund Mol m 2005; 569(1-2>): 29-63.
[23]
Papaioannou A, Chevet E. Driving cancer tumorigenesis and metastasis through UPR signaling. InCoordinating Organismal Physiology Through the Unfolded Protein Response. Springer 2017; 159-92.
[24]
Otamiri T, Sjödahl R. Increased lipid peroxidation in malignant tissues of patients with colorectal cancer. Cancer 1989; 64(2): 422-5.
[http://dx.doi.org/10.1002/1097-0142(19890715)64:2<422::AID-CNCR2820640214>3.0.CO;2-2] [PMID: 2544250]
[25]
Kondo S, Toyokuni S, Tanaka T, et al. Overexpression of the hOGG1 gene and high 8-hydroxy-2′-deoxyguanosine (8-OHdG) lyase activity in human colorectal carcinoma: Regulation mechanism of the 8-OHdG level in DNA. Clin Cancer Res 2000; 6(4): 1394-400.
[PMID: 10778969]
[26]
Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis 2000; 21(3): 361-70.
[http://dx.doi.org/10.1093/carcin/21.3.361] [PMID: 10688856]
[27]
Chang D, Wang F, Zhao YS, Pan HZ. Evaluation of oxidative stress in colorectal cancer patients. Biomed Environ Sci 2008; 21(4): 286-9.
[http://dx.doi.org/10.1016/S0895-3988(08)60043-4] [PMID: 18837290]
[28]
Skrzydlewska E, Kozuszko B, Sulkowska M, et al. Antioxidant potential in esophageal, stomach and colorectal cancers. Hepatogastroenterology 2003; 50(49): 126-31.
[PMID: 12630007]
[29]
Lecot P, Alimirah F, Desprez PY, Campisi J, Wiley C. Context-dependent effects of cellular senescence in cancer development. Br J Cancer 2016; 114(11): 1180-4.
[http://dx.doi.org/10.1038/bjc.2016.115] [PMID: 27140310]
[30]
Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev 2010; 24(22): 2463-79.
[http://dx.doi.org/10.1101/gad.1971610] [PMID: 21078816]
[31]
d’Adda di Fagagna F. Living on a break: Cellular senescence as a DNA-damage response. Nat Rev Cancer 2008; 8(7): 512-22.
[http://dx.doi.org/10.1038/nrc2440] [PMID: 18574463]
[32]
Young AR, Narita M. SASP reflects senescence. EMBO Rep 2009; 10(3): 228-30.
[http://dx.doi.org/10.1038/embor.2009.22] [PMID: 19218920]
[33]
Rodier F, Muñoz DP, Teachenor R, et al. DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion. J Cell Sci 2011; 124(Pt 1): 68-81.
[http://dx.doi.org/10.1242/jcs.071340] [PMID: 21118958]
[34]
Yun MH. Cellular senescence in tissue repair: Every cloud has a silver lining. Int J Dev Biol 2018; 62(8): 591-604.
[35]
Kuilman T, Michaloglou C, Vredeveld LC, et al. Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 2008; 133(6): 1019-31.
[http://dx.doi.org/10.1016/j.cell.2008.03.039] [PMID: 18555778]
[36]
Davalos AR, Coppe JP, Campisi J, Desprez PY. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev 2010; 29(2): 273-83.
[http://dx.doi.org/10.1007/s10555-010-9220-9] [PMID: 20390322]
[37]
Toso A, Revandkar A, Di Mitri D, et al. Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity. Cell Rep 2014; 9(1): 75-89.
[http://dx.doi.org/10.1016/j.celrep.2014.08.044] [PMID: 25263564]
[38]
Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP. Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res 1998; 58(23): 5489-94.
[PMID: 9850084]
[39]
Mazin AL. Life span prediction from the rate of age-related DNA demethylation in normal and cancer cell lines. Exp Gerontol 1995; 30(5): 475-84.
[http://dx.doi.org/10.1016/0531-5565(95)00004-Z] [PMID: 8557095]
[40]
Eden S, Cedar H. Role of DNA methylation in the regulation of transcription. Curr Opin Genet Dev 1994; 4(2): 255-9.
[http://dx.doi.org/10.1016/S0959-437X(05)80052-8] [PMID: 8032203]
[41]
Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 1994; 7(4): 536-40.
[http://dx.doi.org/10.1038/ng0894-536] [PMID: 7951326]
[42]
Issa JPJ, Vertino PM, Boehm CD, Newsham 1 F, Baylin S B. Switch from mono-allelic to bi-allelic human IGF2 promoter methylation during aging and carcinogenesis. Proc Natl Acad Sci USA 1996; 93: 11757-62.
[http://dx.doi.org/10.1073/pnas.93.21.11757] [PMID: 8876210]
[43]
von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci 2002; 27(7): 339-44.
[http://dx.doi.org/10.1016/S0968-0004(02)02110-2] [PMID: 12114022]
[44]
Sampson MJ, Winterbone MS, Hughes JC, Dozio N, Hughes DA. Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes. Diabetes Care 2006; 29(2): 283-9.
[http://dx.doi.org/10.2337/diacare.29.02.06.dc05-1715] [PMID: 16443874]
[45]
Henle ES, Han Z, Tang N, Rai P, Luo Y, Linn S. Sequence-specific DNA cleavage by Fe2+-mediated fenton reactions has possible biological implications. J Biol Chem 1999; 274(2): 962-71.
[http://dx.doi.org/10.1074/jbc.274.2.962] [PMID: 9873038]
[46]
Fraga CG, Shigenaga MK, Park JW, Degan P, Ames BN. Oxidative damage to DNA during aging: 8-hydroxy-2′-deoxyguanosine in rat organ DNA and urine. Proc Natl Acad Sci USA 1990; 87(12): 4533-7.
[http://dx.doi.org/10.1073/pnas.87.12.4533] [PMID: 2352934]
[47]
Allen RG, Tresini M, Keogh BP, Doggett DL, Cristofalo VJ. Differences in electron transport potential, antioxidant defenses, and oxidant generation in young and senescent fetal lung fibroblasts (WI-38). J Cell Physiol 1999; 180(1): 114-22.
[http://dx.doi.org/10.1002/(SICI)1097-4652(199907)180:1<114::AID-JCP13>3.0.CO;2-0] [PMID: 10362024]
[48]
Ramsey MR, Sharpless NE. ROS as a tumour suppressor? Nat Cell Biol 2006; 8(11): 1213-5.
[http://dx.doi.org/10.1038/ncb1106-1213] [PMID: 17077852]
[49]
Bodnar AG, Ouellette M, Frolkis M, et al. Extension of life-span by introduction of telomerase into normal human cells. Science 1998; 279(5349): 349-52.
[http://dx.doi.org/10.1126/science.279.5349.349] [PMID: 9454332]
[50]
d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003; 426(6963): 194-8.
[http://dx.doi.org/10.1038/nature02118] [PMID: 14608368]
[51]
Shiloh Y. The ATM-mediated DNA-damage response: Taking shape. Trends Biochem Sci 2006; 31(7): 402-10.
[http://dx.doi.org/10.1016/j.tibs.2006.05.004] [PMID: 16774833]
[52]
Ciccia A, Elledge SJ. The DNA damage response: Making it safe to play with knives. Mol Cell 2010; 40(2): 179-204.
[http://dx.doi.org/10.1016/j.molcel.2010.09.019] [PMID: 20965415]
[53]
Suram A, Kaplunov J, Patel PL, et al. Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions. EMBO J 2012; 31(13): 2839-51.
[http://dx.doi.org/10.1038/emboj.2012.132] [PMID: 22569128]
[54]
Padayatty SJ, Katz A, Wang Y, et al. Vitamin C as an antioxidant: Evaluation of its role in disease prevention. J Am Coll Nutr 2003; 22(1): 18-35.
[http://dx.doi.org/10.1080/07315724.2003.10719272] [PMID: 12569111]
[55]
Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011; 11(2): 85-95.
[http://dx.doi.org/10.1038/nrc2981] [PMID: 21258394]
[56]
Nikitovic D, Corsini E, Kouretas D, Tsatsakis A, Tzanakakis G. ROS-major mediators of extracellular matrix remodeling during tumor progression. Food Chem Toxicol 2013; 61: 178-86.
[http://dx.doi.org/10.1016/j.fct.2013.06.013] [PMID: 23792086]
[57]
Giannoni E, Parri M, Chiarugi P. EMT and oxidative stress: A bidirectional interplay affecting tumor malignancy. Antioxid Redox Signal 2012; 16(11): 1248-63.
[http://dx.doi.org/10.1089/ars.2011.4280] [PMID: 21929373]
[58]
Bartsch H, Nair J. Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: Role of lipid peroxidation, DNA damage, and repair. Langenbecks Arch Surg 2006; 391(5): 499-510.
[http://dx.doi.org/10.1007/s00423-006-0073-1] [PMID: 16909291]
[59]
Matosevic P, Klepac-Pulanic T, Kinda E, Augustin G, Brcic I, Jakic-Razumovic J. Immunohistochemical expression of 8-oxo-7,8-dihydro-2′-deoxyguanosine in cytoplasm of tumour and adjacent normal mucosa cells in patients with colorectal cancer. J Surg Oncol 2015; 13: 1-9.
[60]
Loft S, Svoboda P, Kasai H, et al. Prospective study of 8-oxo-7,8-dihydro-2′-deoxyguanosine excretion and the risk of lung cancer. Carcinogenesis 2006; 27(6): 1245-50.
[http://dx.doi.org/10.1093/carcin/bgi313] [PMID: 16364924]
[61]
Skrzydlewska E, Sulkowski S, Koda M, Zalewski B, Kanczuga-Koda L, Sulkowska M. Lipid peroxidation and antioxidant status in colorectal cancer. World J Gastroenterol 2005; 11(3): 403-6.
[http://dx.doi.org/10.3748/wjg.v11.i3.403] [PMID: 15637754]
[62]
Brown JR, DuBois RN. COX-2: a molecular target for colorectal cancer prevention. J Clin Oncol 2005; 23(12): 2840-55.
[http://dx.doi.org/10.1200/JCO.2005.09.051] [PMID: 15837998]
[63]
Sebio A, Kahn M, Lenz HJ. The potential of targeting Wnt/β- catenin in colon cancer. Expert Opin Ther Targets 2014; 18(6): 611-5.
[http://dx.doi.org/10.1517/14728222.2014.906580] [PMID: 24702624]
[64]
Moradi-Marjaneh R, Hassanian SM, Mehramiz M, et al. Reactive oxygen species in colorectal cancer: The therapeutic impact and its potential roles in tumor progression via perturbation of cellular and physiological dysregulated pathways. J Cell Physiol 2019; 234(7): 10072-9.
[http://dx.doi.org/10.1002/jcp.27881] [PMID: 30515827]
[65]
Kajla S, Mondol AS, Nagasawa A, et al. A crucial role for Nox 1 in redox-dependent regulation of Wnt-β-catenin signaling. FASEB J 2012; 26(5): 2049-59.
[http://dx.doi.org/10.1096/fj.11-196360] [PMID: 22278940]
[66]
Lei Y, Huang K, Gao C, Lau QC, Pan H, Xie K. Proteomics identification of itgb3 as a key regulator in reactive oxygen species-induced migration and invasion of colorectal cancer cells. Mol Cell Proteom 2011; 2011: 10.
[http://dx.doi.org/10.1074/mcp.M110.005397]
[67]
Wei X, Wang G, Li W, et al. Activation of the JAK-STAT3 pathway is associated with the growth of colorectal carcinoma cells. Oncol Rep 2014; 31(1): 335-41.
[http://dx.doi.org/10.3892/or.2013.2858] [PMID: 24253664]
[68]
Gupta A, Rosenberger SF, Bowden GT. Increased ROS levels contribute to elevated transcription factor and MAP kinase activities in malignantly progressed mouse keratinocyte cell lines. Carcinogenesis 1999; 20(11): 2063-73.
[http://dx.doi.org/10.1093/carcin/20.11.2063] [PMID: 10545407]
[69]
Viennois E, Chen F, Merlin D. NF-κB pathway in colitis-associated cancers. Transl Gastrointest Cancer 2013; 2(1): 21-9.
[PMID: 23626930]
[70]
Wang L, Hitron JA, Wise JTF, et al. Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells. Toxicol Appl Pharmacol 2015; 288(2): 232-9.
[http://dx.doi.org/10.1016/j.taap.2015.07.019] [PMID: 26220687]
[71]
Song NR, Chung MY, Kang NJ, et al. Quercetin suppresses invasion and migration of H-Ras-transformed MCF10A human epithelial cells by inhibiting phosphatidylinositol 3-kinase. Food Chem 2014; 142: 66-71.
[http://dx.doi.org/10.1016/j.foodchem.2013.07.002] [PMID: 24001813]
[72]
Li T, Zhu J, Guo L, Shi X, Liu Y, Yang X. Differential effects of polyphenols-enriched extracts from hawthorn fruit peels and fleshes on cell cycle and apoptosis in human MCF-7 breast carcinoma cells. Food Chem 2013; 141(2): 1008-18.
[http://dx.doi.org/10.1016/j.foodchem.2013.04.050] [PMID: 23790880]
[73]
Sulaiman RS, Basavarajappa HD, Corson TW. Natural product inhibitors of ocular angiogenesis. Exp Eye Res 2014; 129: 161-71.
[http://dx.doi.org/10.1016/j.exer.2014.10.002] [PMID: 25304218]
[74]
Sarubbo F, Moranta D, Asensio VJ, Miralles A, Esteban S. Effects of resveratrol and other polyphenols on the most common brain age-related diseases. Curr Med Chem 2017; 24(38): 4245-66.
[http://dx.doi.org/10.2174/0929867324666170724102743] [PMID: 28738770]
[75]
Tilstra JS, Clauson CL, Niedernhofer LJ, Robbins PD. NF-κB in Aging and Disease. Aging Dis 2011; 2(6): 449-65.
[PMID: 22396894]
[76]
Ursini F, Maiorino M, Morazzoni P, Roveri A, Pifferi G. A novel antioxidant flavonoid (IdB 1031) affecting molecular mechanisms of cellular activation. Free Radic Biol Med 1994; 16(5): 547-53.
[http://dx.doi.org/10.1016/0891-5849(94)90054-X] [PMID: 8026797]
[77]
Paramita P, Subramaniam VD, Murugesan R, et al. Evaluation of potential anti-cancer activity of cationic liposomal nanoformulated Lycopodium clavatum in colon cancer cells. IET Nanobiotechnol 2018; 12(6): 727-32.
[http://dx.doi.org/10.1049/iet-nbt.2017.0106] [PMID: 30104445]
[78]
Kiokias S, Gordon MH. Antioxidant properties of carotenoids in vitro and in vivo. Food Rev Int 2004; 20(2): 99-121.
[http://dx.doi.org/10.1081/FRI-120037155]
[79]
Forster GM, Raina K, Kumar A, et al. Rice varietal differences in bioactive bran components for inhibition of colorectal cancer cell growth. Food Chem 2013; 141(2): 1545-52.
[http://dx.doi.org/10.1016/j.foodchem.2013.04.020] [PMID: 23790950]
[80]
Bagi Z, Cseko C, Tóth E, Koller A. Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment. Am J Physiol Heart Circ Physiol 2003; 285(6): H2277-83.
[http://dx.doi.org/10.1152/ajpheart.00448.2003] [PMID: 12869370]
[81]
Upritchard JE, Schuurman CR, Wiersma A, et al. Spread supplemented with moderate doses of vitamin E and carotenoids reduces lipid peroxidation in healthy, nonsmoking adults. Am J Clin Nutr 2003; 78(5): 985-92.
[http://dx.doi.org/10.1093/ajcn/78.5.985] [PMID: 14594786]
[82]
Niki E, Noguchi N, Tsuchihashi H, Gotoh N. Interaction among vitamin C, vitamin E, and beta-carotene. Am J Clin Nutr 1995; 62(6)(Suppl.): 1322S-6S.
[http://dx.doi.org/10.1093/ajcn/62.6.1322S] [PMID: 7495227]
[83]
Vucenik I, Shamsuddin AM. Cancer inhibition by inositol hexaphosphate (IP6) and inositol: From laboratory to clinic. J Nutr 2003; 133(11)(Suppl. 1): 3778S-84S.
[http://dx.doi.org/10.1093/jn/133.11.3778S] [PMID: 14608114]

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