Vitamin A in prevention and treatment of cancer

  • Authors

    • Ricardo Carvalho Post-graduate Program in Pharmaceutical Science, Federal University of Piauí, Teresina, Piauí, Brazil
    • Muhammad Islam Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina (Piauí)-64.049-550, Brazil.
    • Ana Mata Post-graduate Program in Pharmaceutical Science, Federal University of Piauí, Teresina, Piauí, Brazil
    • Reyca e Silva Laboratory of Treatment of Materials, Federal Institute of Piauí, Teresina, Piauí, Brazil
    • Márcia Paz Post-graduate Program in Pharmaceutical Science, Federal University of Piauí, Teresina, Piauí, Brazil
    • Marcus Alencar Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina (Piauí)-64.049-550, Brazil.
    • Hercília Rolim Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina (Piauí)-64.049-550, Brazil.
    • Maria Medeiros Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina (Piauí)-64.049-550, Brazil.
    • João e Sousa Department of Biological Sciences, Federal University of Piauí, Picos (Piauí), 64.607-670, Brazil.
    • Ana Amélia Melo-Cavalcante Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina (Piauí)-64.049-550, Brazil.
    2017-07-16
    https://doi.org/10.14419/ijm.v5i2.7947
  • , Vitamin A, Oxidative Stress, Cancer.

  • Abstract

    Dietary components not only act as chemo preventive agents but also risk factors in the onset of cancer, which stimulating nutritional bal-ance in cancer or non-cancer populations. The supplementation of antioxidant compounds, such as vitamin A (Vit A) and few of its deriva-tives has been reported to alleviate the oxidative stress in cancer patients. This review focuses on sketching a current scenario on the Vit A role in cancer prevention and therapy. Therefore, we searched for published article on PubMed and Science Direct between 2014 and 2015. The search yielded 75 articles related to Vit A-mediated anti-oxidative or pro-oxidative effects in cancer patients. A low dose-mediated anti-cancer effect was observed with Vit A in some cancers. The clinical studies showed discrepancies between the low and high doses of Vit A in cancer. In conclusion, precautions are needed in taking Vit A and its derivatives, especially in cancer.

  • References

    1. [1] Alabdali A, Al-Ayadhi L, El-Ansary A. 2014. A key role for an impaired detoxification mechanism in the etiology and severity of autism spectrum disorders. Behav. Brain. Funct. 10:14. https://doi.org/10.1186/1744-9081-10-14.
      [2] Ameri A, Alidoosti A, Hosseini Y, Parvin M, Emranpour MH, Taslimi F, et al. 2011. Prognostic value of promoter hypermethylation of Retinoic Acid Receptor Beta (RARB) and CDKN2 (p16/MTS1) in prostate cancer. Chinese J. Cancer Res. 23:306-311. https://doi.org/10.1007/s11670-011-0306-x.
      [3] Apraiz A, Boyano MD, Asumendi A. 2011. Cell-centric view of apoptosis and apoptotic cell death-inducing antitumoral strategies. Cancers (Basel) 3:1042-1080. https://doi.org/10.3390/cancers3011042.
      [4] Barber T, Esteban-Pretel G, Marín M, Timoneda J. 2014. Vitamin A Deficiency and Alterations in the Extracellular Matrix. Nutri. 6:4984-5017. https://doi.org/10.3390/nu6114984.
      [5] Behr GA, Schnorr CE, Simoes-Pires A, Da Motta LL, Frey BN, Moreira JCF. 2012. Increased cerebral oxidative damage and decreased antioxidant defenses in ovariectomized and sham-operated rats supplemented with vitamin A. Cell Biol. Toxicol. 28:317-330. https://doi.org/10.1007/s10565-012-9226-x.
      [6] Bjelakovic G, Nikolova D, Gluud C. 2013a. Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm? PLoS One 8:e74558. https://doi.org/10.1371/journal.pone.0074558.
      [7] Bjelakovic G, Nikolova D, Gluud C. 2013b. Antioxidant Supplements to Prevent Mortality. JAMA 310:1178-1179. https://doi.org/10.1001/jama.2013.277028.
      [8] Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. 2007. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 297:842-857. https://doi.org/10.1001/jama.297.8.842.
      [9] Bowry VW, Ingoldt KU, Stocker R. 1992. Vitamin E in human low-density lipoprotein. Biochem. J. 288:341-344. https://doi.org/10.1042/bj2880341.
      [10] Bozzetti F. 2015. Evidence-based nutritional support of the elderly cancer patient. Nutri. 31:585-586. https://doi.org/10.1016/j.nut.2014.11.004.
      [11] Brown GT, Cash BG, Blihoghe D, Johansson P, Alnabulsi A, Murray GI. 2014. The expression and prognostic significance of retinoic acid metabolising enzymes in colorectal cancer. PLoS One 9:1-13. https://doi.org/10.1371/journal.pone.0090776.
      [12] Bucioli SA, De Abreu L, Valenti VE, Leone C, Vannucchi H. 2011. Effects of vitamin E supplementation on renal non-enzymatic antioxidants in young rats submitted to exhaustive exercise stress. BMC Complement. Altern. Med. 11:133. https://doi.org/10.1186/1472-6882-11-133.
      [13] Bushue N, Wan YY. 2010. Retinoid pathway and cancer therapeutics ☆. Adv. Drug Deliv. Rev. 62:1285-1298. https://doi.org/10.1016/j.addr.2010.07.003.
      [14] Carmona-Gutiérrez D, Bauer MA, Ring J, Knauer H, Eisenberg T, Büttner S, et al. 2011. The propeptide of yeast cathepsin D inhibits programmed necrosis. Cell Death Dis. 2:e161. https://doi.org/10.1038/cddis.2011.43.
      [15] Carrera S, Cuadrado-Castano S, Samuel J, Jones GDD, Villar E, Lee SW, Macip S. 2013. Stra6, a retinoic acid-responsive gene, participates in p53-induced apoptosis after DNA damage. Cell Death Differ. 20:910-919. https://doi.org/10.1038/cdd.2013.14.
      [16] Celik VK, Eken IE, Yildiz G, Yilmaz MB, Gurlek A, Aydin H. 2013. Vitamin E and antioxidant activity; its role in slow coronary flow. Cardiovasc. J. Afr. 24:360-363. https://doi.org/10.5830/CVJA-2013-076.
      [17] Chang H, Sheen L, Lei Y. 2015. The protective role of carotenoids and polyphenols in patients with head and neck cancer. J. Chinese Med. Assoc. 78:89-95. https://doi.org/10.1016/j.jcma.2014.08.010.
      [18] Chen M-C, Huang C-Y, Hsu S-L, Lin E, Ku C-T, Lin H, Chen C-M. 2012. Retinoic Acid Induces Apoptosis of Prostate Cancer DU145 Cells through Cdk5 Overactivation. Evid. Based Complement. Alternat. Med. 2012:580736. https://doi.org/10.1155/2012/580736.
      [19] Chen Y-C, Prabhu KS, Mastro AM. 2013. Is selenium a potential treatment for cancer metastasis? Nutri. 5:1149-1168. https://doi.org/10.3390/nu5041149.
      [20] Cheng TYD, Goodman GE, Thornquist MD, Barnett MJ, Beresford SAA, Lacroix AZ, et al. 2014. Estimated intake of vitamin D and its interaction with vitamin A on lung cancer risk among smokers. Int. J. Cancer 135:2135-2145. https://doi.org/10.1002/ijc.28846.
      [21] Circu ML, Aw TY. 2012. Glutathione and modulation of cell apoptosis. Biochim. Biophys. Acta 1823:1767-1777. https://doi.org/10.1016/j.bbamcr.2012.06.019.
      [22] Clamon G. 2015. Chemoprevention and Screening for Lung Cancer : Changing Our Focus to Former Smokers. Clin. Lung Cancer 16:1-5. https://doi.org/10.1016/j.cllc.2014.09.009.
      [23] Clouser MC, Roe DJ, Foote JA, Harris RB, Alberts DS. 2010. Dose Response of Retinol and Isotretinoin in the Prevention of Nonmelanoma Skin Cancer Recurrence Dose Response of Retinol and Isotretinoin in the Prevention of Nonmelanoma Skin Cancer Recurrence. Nutr. Cancer. 62:1058-1066. https://doi.org/10.1080/01635581.2010.492089.
      [24] Colacino JA, Arthur AE, Dolinoy DC, Sartor MA, Duffy SA, Chepeha DB, et al. 2012. Pretreatment dietary intake is associated with tumor suppressor DNA methylation in head and neck squamous cell carcinomas. Epigenetics 7:883-891. https://doi.org/10.4161/epi.21038.
      [25] Connolly R, Nguyen N, Sukumar S. 2013. Molecular pathways: current role and future directions of the retinoic acid pathway in cancer prevention and treatment. Clin. Cancer Res. 19:1651-1659. https://doi.org/10.1158/1078-0432.CCR-12-3175.
      [26] Cook-Mills JM, Abdala-Valencia H, Hartert T. 2013. Two faces of vitamin e in the lung. Am. J. Respir. Crit. Care Med. 188:279-284. https://doi.org/10.1164/rccm.201303-0503ED.
      [27] Coulter ID, Hardy ML, Morton SC, Hilton LG, Tu W, Valentine D, Shekelle PG. 2006. Antioxidants Vitamin C and Vitamin E for the Prevention and Treatment of Cancer. Cancer 2138:735-744. https://doi.org/10.1111/j.1525-1497.2006.00483.x.
      [28] De Oliveira MR, Moreira JCF. 2007. Acute and chronic vitamin A supplementation at therapeutic doses induces oxidative stress in submitochondrial particles isolated from cerebral cortex and cerebellum of adult rats. Toxicol. Lett. 173:145-150. https://doi.org/10.1016/j.toxlet.2007.07.002.
      [29] De Oliveira MR, Moreira JCF. 2008. Impaired redox state and respiratory chain enzyme activities in the cerebellum of vitamin A-treated rats. Toxicol. 253:125-130. https://doi.org/10.1016/j.tox.2008.09.003.
      [30] De Oliveira MR, Oliveira MWS, Da Rocha RF, Moreira JCF. 2009. Vitamin A supplementation at pharmacological doses induces nitrosative stress on the hypothalamus of adult Wistar rats. Chem.-Biol. Interact. 180:407-413. https://doi.org/10.1016/j.cbi.2009.02.006.
      [31] Demaria S, Pikarsky E, Karin M, Coussens LM, Chen Y-C, El-Omar EM, et al. 2010. Cancer and inflammation: promise for biologic therapy. J. Immunother. 33:335-351. https://doi.org/10.1097/CJI.0b013e3181d32e74.
      [32] Doldo E, Costanza G, Agostinelli S, Tarquini C, Ferlosio A, Arcuri G, et al. 2015. Vitamin A, Cancer Treatment and Prevention: The New Role of Cellular Retinol Binding Proteins. Biomed. Res. Int. 2015:1-14. https://doi.org/10.1155/2015/624627.
      [33] Donkena KV, Karnes RJ, Young CYF. 2010. Vitamins and Prostate Cancer Risk. Mayo Clinic 15:1762-1783. https://doi.org/10.3390/molecules15031762.
      [34] Dorjgochoo T, Shrubsole MJ, Shu XO, Lu W, Ruan Z, Zheng Y, et al. 2008. Vitamin supplement use and risk for breast cancer: The Shanghai breast cancer study. Breast Cancer Res. Treat. 111:269-278. https://doi.org/10.1007/s10549-007-9772-8.
      [35] Fernández-Calotti PX, Lopez-Guerra M, Colomer D, Pastor-Anglada M. 2012. Enhancement of fludarabine sensitivity by all-trans-retinoic acid in chronic lymphocytic leukemia cells. Haematologica 97:943-951. https://doi.org/10.3324/haematol.2011.051557.
      [36] Flodrova D, Benkovska D, Macejova D, Bialesova L, Hunakova L, Brtko J, Bobalova J. 2015. Proteomic analysis of changes in the protein composition of MCF-7 human breast cancer cells induced by all-trans retinoic acid, 9-cis retinoic acid, and their combination. Toxicol. Lett. 232:226-232. https://doi.org/10.1016/j.toxlet.2014.09.030.
      [37] Greenlee H. 2012. Natural Products for Cancer Prevention. Semin. Oncol. Nurs. 28:29-44. https://doi.org/10.1016/j.soncn.2011.11.004.
      [38] Grune T, Lietz G, Palou A, Ross AC, Stahl W, Tang G, et al. 2010. Beta-carotene is an important vitamin A source for humans. J. Nutr. 140:2268S-2285S. https://doi.org/10.3945/jn.109.119024.
      [39] Guan J, Zhang H, Wen Z, Gu Y, Cheng Y, Sun Y, et al. 2014. Retinoic acid inhibits pancreatic cancer cell migration and EMT through the downregulation of IL-6 in cancer associated fibroblast cells. Cancer Lett. 345:132-139. https://doi.org/10.1016/j.canlet.2013.12.006.
      [40] Guicciardi ME, Malhi H, Mott JL, Gores GJ. 2013. Apoptosis and Necrosis in the Liver Maria. Compr. Physiol. 3:2.
      [41] Guo R. 2011. Rosiglitazone and retinoic acid inhibit proliferation and induce apoptosis in the HCT-15 human colorectal cancer cell line. Exp. Ther. Med. 2011:413-417. https://doi.org/10.3892/etm.2011.227.
      [42] Hang J, Chen Y-H, Lu Q. 2010. Pro-oncogenic and anti-oncogenic pathways: opportunities and challenges of cancer therapy. Future Oncol. 6:587-603. https://doi.org/10.2217/fon.10.15.
      [43] Heo S-H, Kwak J, Jang KL. 2015. All-trans retinoic acid induces p53-depenent apoptosis in human hepatocytes by activating p14 expression via promoter hypomethylation. Cancer Lett. 362:139-148. https://doi.org/10.1016/j.canlet.2015.03.036.
      [44] Holmes D, Vishnu P, Dorer RK, Aboulafia DM. 2012. All-Trans Retinoic Acid-Induced Pseudotumor Cerebri during Induction Therapy for Acute Promyelocytic Leukemia: A Case Report and Literature Review. Case Rep. Oncol. Med. 2012:1-11. https://doi.org/10.1155/2012/313057.
      [45] Hong S-D, Kim Y-K, Kim H-N, Lee SR, Ahn J-S, Yang D-H, et al. 2011. Treatment outcome of all-trans retinoic acid/anthracycline combination chemotherapy and the prognostic impact of FLT3/ITD mutation in acute promyelocytic leukemia patients. Korean J. Hematol. 46:24-30. https://doi.org/10.5045/kjh.2011.46.1.24.
      [46] Hsu K-H, Carbia BE, Plummer C, Chauhan A. 2015. Dual Drug Delivery from Vitamin E loaded Contact Lenses for Glaucoma Therapy. Eur. J. Pharm. Biopharm. 94:312-321. https://doi.org/10.1016/j.ejpb.2015.06.001.
      [47] Ionta M, Rosa MC, Almeida RB, Freitas VM, Rezende-Teixeira P, Machado-Santelli GM. 2012. Retinoic acid and cAMP inhibit rat hepatocellular carcinoma cell proliferation and enhance cell differentiation. Braz. J. Med. Biol. Res. 45:721-729. https://doi.org/10.1590/S0100-879X2012007500087.
      [48] Johansson AC, Appelqvist H, Nilsson C, Kågedal K, Roberg K, Öllinger K. 2010. Regulation of apoptosis-associated lysosomal membrane permeabilization. Apoptosis 15:527-540. https://doi.org/10.1007/s10495-009-0452-5.
      [49] Johnson DE, Redner RL. 2015. An ATRActive future for differentiation therapy in AML. Blood Rev. 2015:10-15. https://doi.org/10.1016/j.blre.2015.01.002.
      [50] Khan S, Wall D, Curran C, Newell J, Kerin MJ, Dwyer RM. 2015. MicroRNA-10a is reduced in breast cancer and regulated in part through retinoic acid. BMC Cancer 15:1-8. https://doi.org/10.1186/s12885-015-1374-y.
      [51] Khillan JS. 2014. Vitamin A/retinol and maintenance of Pluripotency of stem cells. Nutri. 6:1209-1222. https://doi.org/10.3390/nu6031209.
      [52] Kong P, Cai Q, Geng Q, Wang J, Lan Y, Zhan Y, Xu D. 2014. Vitamin Intake Reduce the Risk of Gastric Cancer: Meta-Analysis and Systematic Review of Randomized and Observational Studies. PLoS One 9:e116060. https://doi.org/10.1371/journal.pone.0116060.
      [53] Lee JH, Kishikawa M, Kumazoe M, Yamada K, Tachibana H. 2010. Vitamin A enhances antitumor effect of a green tea polyphenol on melanoma by upregulating the polyphenol sensing molecule 67-kDa laminin receptor. PLoS One 5:1-8. https://doi.org/10.1371/journal.pone.0011051.
      [54] Lee SI, Yun J, Baek J, Jeong Y, Kim J, Kang JS, Park SH, Kim SK, Park S. 2015. NgR1 Expressed in P19 Embryonal Carcinoma Cells Differentiated by Retinoic Acid Can Activate STAT3. Korean J. Physiol. Pharmacol. 19:105-109. https://doi.org/10.4196/kjpp.2015.19.2.105.
      [55] Li X, Ashana AO, Moretti VM, Lackman RD. 2011. The relation of tumour necrosis and survival in patients with osteosarcoma. Int. Orthop. 35:1847-1853. https://doi.org/10.1007/s00264-011-1209-7.
      [56] Liu X, Cai H, Huang H, Long Z, Shi Y, Wang Y. 2011. The prognostic significance of apoptosis-related biological markers in chinese gastric cancer patients. PLoS One 6:1-8. https://doi.org/10.1371/journal.pone.0029670.
      [57] Lqubal MA, Khan M, Kumar P, Kumar A, Ajai K. 2014. Role of Vitamin E in Prevention of Oral Cancer:-A Review. J. Clin. Diagnostic. Res. 8:5-7. https://doi.org/10.7860/jcdr/2014/9166.4958.
      [58] Mactier H, Weaver LT. 2005. Vitamin A and preterm infants: what we know, what we don’t know, and what we need to know. Arch. Dis. Child Fetal Neonatal Ed. 90:F103-F108.
      [59] Mahalingam D, Natoni A, Keane M, Samali A, Szegezdi E. 2010. Early growth response-1 is a regulator of DR5-induced apoptosis in colon cancer cells. Br. J. Cancer 102:754-764. https://doi.org/10.1038/sj.bjc.6605545.
      [60] Marcato P, Dean CA, Liu RZ, Coyle KM, Bydoun M, Wallace M, et al. 2014. Aldehyde dehydrogenase 1A3 influences breast cancer progression via differential retinoic acid signaling. Mol. Oncol. 9:17-31. https://doi.org/10.1016/j.molonc.2014.07.010.
      [61] Meloni M. 2014. The social brain meets the reactive genome: neuroscience, epigenetics and the new social biology. Front Hum. Neurosci. 8:309.
      [62] Moquin D, Chan F. 2010. The molecular regulation of programmed necrotic cell injury. Trends Biochem. Sci. 35:434-441. https://doi.org/10.1016/j.tibs.2010.03.001.
      [63] Neuzil J, Tomasetti M, Zhao Y, Dong L-F, Birringer M, Wang X-F, et al. 2007. E analogs, a novel group of “mitocans,†as anticancer agents: the importance of being redox-silent. Mol. Pharmacol. 71:1185-1199. https://doi.org/10.1124/mol.106.030122.
      [64] Nicolau-Galmés F, Asumendi A, Alonso-Tejerina E, Pérez-Yarza G, Jangi SM, Gardeazabal J, et al. 2011. Terfenadine induces apoptosis and autophagy in melanoma cells through ROS-dependent and -independent mechanisms. Apoptosis 16:1253-1267. https://doi.org/10.1007/s10495-011-0640-y.
      [65] Oliveira MR. 2015. Vitamin A and Retinoids as Mitochondrial Toxicants. Oxidat. Med. Cellul. Longev. 2015.
      [66] Oliveira MR, Da Rocha RF, Pasquali MADB, Moreira JCF. 2012. The effects of vitamin A supplementation for 3 months on adult rat nigrostriatal axis: Increased monoamine oxidase enzyme activity, mitochondrial redox dysfunction, increased β-amyloid 1-40 peptide and TNF-α contents, and susceptibili. Brain Res. Bull. 87:432-444. https://doi.org/10.1016/j.brainresbull.2012.01.005.
      [67] Oliveira MR, Oliveira MWS, Behr GA, Moreira JCF. 2009. Vitamin A supplementation at clinical doses induces a dysfunction in the redox and bioenergetics states, but did change neither caspases activities nor TNF-?? levels in the frontal cortex of adult Wistar rats. J. Psychiatr. Res. 43:754-762. https://doi.org/10.1016/j.jpsychires.2008.10.002.
      [68] Park JH, Qiao B, Panageas KS, Schymura MJ, Jurcic JG, Rosenblat TL, et al. 2011. Early death rate in acute promyelocytic leukemia remains high despite all- trans retinoic acid. Blood 118:1248-1255. https://doi.org/10.1182/blood-2011-04-346437.
      [69] Park Y, Spiegelman D, Hunter DJ, Albanes D, Bergkvist L, Buring JE, et al. 2010. Intakes of vitamins A , C , and E and use of multiple vitamin supplements and risk of colon cancer : a pooled analysis of prospective cohort studies. Cancer Causes Contr. 21:1745-1757. https://doi.org/10.1007/s10552-010-9549-y.
      [70] Qiao J, Paul P, Lee S, Qiao L, Josifi E, Tiao JR, Chung DH. 2012. PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation. Biochem. Biophys. Res. Commun. 424:421-426. https://doi.org/10.1016/j.bbrc.2012.06.125.
      [71] Rochette-Egly C. 2015. Biochimica et Biophysica Acta Retinoic acid signaling and mouse embryonic stem cell differentiation : Cross talk between genomic and non-genomic effects of RA ☆. BBA – Mol. Cell Biol. Lipids 1851:66-75. https://doi.org/10.1016/j.bbalip.2014.04.003.
      [72] Sadowska-Bartosz I, Bartosz G. 2014. Effect of antioxidants supplementation on aging and longevity. Biomed. Res. Int. 2014:404680.
      [73] Schnorr CE, Morrone MDS, Weber MH, Lorenzi R, Behr GA, Moreira JCF. 2011. The effects of vitamin A supplementation to rats during gestation and lactation upon redox parameters: Increased oxidative stress and redox modulation in mothers and their offspring. Food Chem. Toxicol. 49:2645-2654. https://doi.org/10.1016/j.fct.2011.07.010.
      [74] Schnorr C, Morrone M, Simões-Pires A, Bittencourt L, Zeidán-Chuliá F, Moreira J. 2014. Supplementation of Adult Rats with Moderate Amounts of β-Carotene Modulates the Redox Status in Plasma without Exerting Pro-Oxidant Effects in the Brain: A Safer Alternative to Food Fortification with Vitamin A? Nutri. 6:5572-5582. https://doi.org/10.3390/nu6125572.
      [75] Shukla S, Meeran SM, Katiyar SK. 2014. Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention. Cancer Lett. 355:9-17. https://doi.org/10.1016/j.canlet.2014.09.017.
      [76] Suntharalingam K, Song Y, Lippard SJ. 2014. Conjugation of vitamin E analog α-TOS to Pt(IV) complexes for dual-targeting anticancer therapy. Chem. Commun. (Camb) 50:2465-2468. https://doi.org/10.1039/c3cc48740g.
      [77] Szabo E, Mao JT, Lam S, Reid ME, Keith RL. 2013. Chemoprevention of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American college of chest physicians evidence-based clinical practice guidelines. Chest 2013:143.
      [78] Tang J-E, Wang R-J, Zhong H, Yu B, Chen Y. 2014. Vitamin A and risk of bladder cancer: a meta-analysis of epidemiological studies. World J. Surg. Oncol. 12:130.
      [79] Tykwinska K, Lauster R, Knaus P, Rosowski M. 2013. Growth and Differentiation Factor 3 Induces Expression of Genes Related to Differentiation in a Model of Cancer Stem Cells and Protects Them from Retinoic Acid-Induced Apoptosis. PLoS One 2013:8.
      [80] Uchino Y, Iriyama N, Hatta Y, Takei M. 2015. Granulocyte colony-stimulating factor potentiates all-trans retinoic acid-induced granulocytic differentiation in acute promyelocytic leukemia cell line HT93A. Cancer Cell Int. 15:1-11. https://doi.org/10.1186/s12935-015-0176-2.
      [81] Varshosaz J, Sadeghi-Aliabadi H, Ghasemi S, Behdadfar B. 2013. Use of magnetic folate-dextran-retinoic acid micelles for dual targeting of doxorubicin in breast cancer. Biomed. Res. Int. 2013.
      [82] Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM. 2012. P53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell 149:1536-1548. https://doi.org/10.1016/j.cell.2012.05.014.
      [83] Von Lintig J. 2012. Provitamin A metabolism and functions in mammalian biology. Am. J. Clin. Nutri. 96:1234-1244. https://doi.org/10.3945/ajcn.112.034629.
      [84] Watters KM, Bryan K, Foley NH, Meehan M, Stallings RL. 2013. Expressional alterations in functional ultra-conserved non-coding RNAs in response to all-trans retinoic acid--induced differentiation in neuroblastoma cells. BMC Cancer 13:184.
      [85] Wensveen FM, Alves NL, Derks IAM, Reedquist KA, Eldering E. 2011. Apoptosis induced by overall metabolic stress converges on the Bcl-2 family proteins Noxa and Mcl-1. Apoptosis 16:708-721. https://doi.org/10.1007/s10495-011-0599-8.
      [86] Wong M, Lodge JK. 2012. A metabolomic investigation of the effects of vitamin E supplementation in humans. Nutr. Metab. (Lond) 9:1.
      [87] Yang Z. 2015. Vitamin E Intake and Pancreatic Cancer Risk: A Meta-Analysis of Observational Studies. Med. Sci. Monit. 21:1249-1255. https://doi.org/10.12659/MSM.893792.
      [88] Zanon-Moreno V, Asensio-Marquez EM, Ciancotti-Oliver L, Garcia-Medina JJ, Ortega-Azorin C, Pinazo-Duran MD, et al. 2013. Effects of polymorphisms in vitamin E-, vitamin C-, and glutathione peroxidase-related genes on serum biomarkers and associations with glaucoma. Molecul. Vision 19:231-242.
      [89] Zanotto-Filho A, Gelain DP, Schröder R, Souza LF, Pasquali MAB, Klamt F, Moreira JCF. 2009. The NFκB-mediated control of RS and JNK signaling in vitamin A-treated cells: Duration of JNK-AP-1 pathway activation may determine cell death or proliferation. Biochem. Pharmacol. 77:1291-1301. https://doi.org/10.1016/j.bcp.2008.12.010.
      [90] Zeegers MP, Goldbohm RA, Van Den Brandt PA. 2001. Are retinol, vitamin C, vitamin E, folate and carotenoids intake associated with bladder cancer risk? Results from the Netherlands Cohort Study. Br. J. Cancer 85:977-983. https://doi.org/10.1054/bjoc.2001.1968.
      [91] Zhang L, Zhou Q, Zhang N, Li W, Ying M, Ding W, Yang B, He Q. 2014. E2F1 impairs all-trans retinoic acid-induced osteogenic differentiation of osteosarcoma via promoting ubiquitination-mediated degradation of RARα. Cell Cycle 13:1277-1287. https://doi.org/10.4161/cc.28190.
      [92] Zhang Y-P, Chu R-X, Liu H. 2014. Vitamin A Intake and Risk of Melanoma: A Meta-Analysis. PLoS One 9:e102527.

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    Carvalho, R., Islam, M., Mata, A., e Silva, R., Paz, M., Alencar, M., Rolim, H., Medeiros, M., e Sousa, J., & Melo-Cavalcante, A. A. (2017). Vitamin A in prevention and treatment of cancer. International Journal of Medicine, 5(2), 199-205. https://doi.org/10.14419/ijm.v5i2.7947

    Received date: 2017-06-07

    Accepted date: 2017-07-07

    Published date: 2017-07-16