The Relationship Between Vitamin B6, Diabetes and Cancer

Chiara Merigliano, Elisa Mascolo, Romina Burla, Isabella Saggio, Fiammetta Vernì, Chiara Merigliano, Elisa Mascolo, Romina Burla, Isabella Saggio, Fiammetta Vernì

Abstract

Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, works as cofactor in numerous enzymatic reactions and it behaves as antioxidant molecule. PLP deficiency has been associated to many human pathologies including cancer and diabetes and the mechanism behind this connection is now becoming clearer. Inadequate intake of this vitamin increases the risk of many cancers; furthermore, PLP deprivation impairs insulin secretion in rats, whereas PLP supplementation prevents diabetic complications and improves gestational diabetes. Growing evidence shows that diabetes and cancer are correlated not only because they share same risk factors but also because diabetic patients have a higher risk of developing tumors, although the underlying mechanisms remain elusive. In this review, we will explore data obtained in Drosophila revealing the existence of a connection between vitamin B6, DNA damage and diabetes, as flies in the past decade turned out to be a promising model also for metabolic diseases including diabetes. We will focus on recent studies that revealed a specific role for PLP in maintaining chromosome integrity and glucose homeostasis, and we will show that these aspects are correlated. In addition, we will discuss recent data identifying PLP as a putative linking factor between diabetes and cancer.

Keywords: AGEs; Drosophila; chromosome aberrations; diabetes; pyridoxal 5′- phosphate; vitamin B6.

References

    1. Aguilera A., Gomez-Gonzalez B. (2008). Genome instability: a mechanistic view of its causes and consequences. Nat. Rev. Genet. 9 204–217. 10.1038/nrg2268
    1. Ahn H. J., Min K. W., Cho Y. O. (2011). Assessment of vitamin B(6) status in Korean patients with newly diagnosed type 2 diabetes. Nutr. Res. Pract. 5 34–39. 10.4162/nrp.2011.5.1.34
    1. Alfa R. W., Kim S. K. (2016). Using drosophila to discover mechanisms underlying type 2 diabetes. Dis. Model. Mech. 9 365–376. 10.1242/dmm.023887
    1. Ames B. N., Wakimoto P. (2002). Are vitamin and mineral deficiencies a major cancer risk? Nat. Rev. Cancer 2 694–704. 10.1038/nrc886
    1. Anand S., Nath B., Saraswathy R. (2014). Diabetes–increased risk for cancers through chromosomal aberrations? Asian Pac. J. Cancer Prev. 15 4571–4573.
    1. Bennink H. J., Schreurs W. H. (1975). Improvement of oral glucose tolerance in gestational diabetes by pyridoxine. Br. Med. J. 3 13–15. 10.1136/bmj.3.5974.13
    1. Bianchi F. T., Tocco C., Pallavicini G., Liu Y., Verni F., Merigliano C., et al. (2017). Citron kinase deficiency leads to chromosomal instability and TP53-sensitive microcephaly. Cell Rep. 18 1674–1686. 10.1016/j.celrep.2017.01.054
    1. Blasiak J., Arabski M., Krupa R., Wozniak K., Zadrozny M., Kasznicki J., et al. (2004). DNA damage and repair in type 2 diabetes mellitus. Mutat. Res. 554 297–304. 10.1016/j.mrfmmm.2004.05.011
    1. Booth A. A., Khalifah R. G., Todd P., Hudson B. G. (1997). In vitro kinetic studies of formation of antigenic advanced glycation end products (AGEs). novel inhibition of post-amadori glycation pathways. J. Biol. Chem. 272 5430–5437. 10.1074/jbc.272.9.5430
    1. Boucher J., Kleinridders A., Kahn C. R. (2014). Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb. Perspect. Biol. 6:a009191. 10.1101/cshperspect.a009191
    1. Brownlee M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature 414 813–820. 10.1038/414813a
    1. Bunting S. F., Nussenzweig A. (2013). End-joining, translocations and cancer. Nat. Rev. Cancer 13 443–454. 10.1038/nrc3537
    1. Clayton P. T. (2006). B6-responsive disorders: a model of vitamin dependency. J. Inherit. Metab. Dis. 29 317–326. 10.1007/s10545-005-0243-2
    1. Cohen K. L., Gorecki G. A., Silverstein S. B., Ebersole J. S., Solomon L. R. (1984). Effect of pyridoxine (vitamin B6) on diabetic patients with peripheral neuropathy. J. Am. Podiatry Assoc. 74 394–397. 10.7547/87507315-74-8-394
    1. Dankner R., Boffetta P., Balicer R. D., Boker L. K., Sadeh M., Berlin A., et al. (2016). Time-Dependent risk of cancer after a diabetes diagnosis in a cohort of 2.3 Million adults. Am. J. Epidemiol. 183 1098–1106. 10.1093/aje/kwv290
    1. di Salvo M. L., Contestabile R., Safo M. K. (2011). Vitamin B(6) salvage enzymes: mechanism, structure and regulation. Biochim. Biophys. Acta 1814 1597–1608. 10.1016/j.bbapap.2010.12.006
    1. di Salvo M. L., Safo M. K., Contestabile R. (2012). Biomedical aspects of pyridoxal 5′-phosphate availability. Front. Biosci. 4 897–913.
    1. Ehrenshaft M., Bilski P., Li M. Y., Chignell C. F., Daub M. E. (1999). A highly conserved sequence is a novel gene involved in de novo vitamin B6 biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 96 9374–9378. 10.1073/pnas.96.16.9374
    1. Ellis J. M., Folkers K., Minadeo M., VanBuskirk R., Xia L. J., Tamagawa H. (1991). A deficiency of vitamin B6 is a plausible molecular basis of the retinopathy of patients with diabetes mellitus. Biochem. Biophys. Res. Commun. 179 615–619. 10.1016/0006-291X(91)91416-A
    1. Florio R., di Salvo M. L., Vivoli M., Contestabile R. (2011). Serine hydroxymethyltransferase: a model enzyme for mechanistic, structural, and evolutionary studies. Biochim. Biophys. Acta 1814 1489–1496. 10.1016/j.bbapap.2010.10.010
    1. Galluzzi L., Vitale I., Senovilla L., Olaussen K. A., Pinna G., Eisenberg T., et al. (2012). Prognostic impact of vitamin B6 metabolism in lung cancer. Cell Rep. 2 257–269. 10.1016/j.celrep.2012.06.017
    1. Garofalo R. S. (2002). Genetic analysis of insulin signaling in Drosophila. Trends Endocrinol. Metab. 13 156–162. 10.1016/S1043-2760(01)00548-3
    1. Gatti M., Goldberg M. L. (1991). Mutations affecting cell division in Drosophila. Methods Cell Biol. 35 543–586. 10.1016/S0091-679X(08)60587-7
    1. Gatti M., Tanzarella C., Olivieri G. (1974). Variation with sex of irradiation-induced chromosome damage in somatic cells of Drosophila melanogaster. Nature 247 151–152. 10.1038/247151a0
    1. Goodarzi M. T., Navidi A. A., Rezaei M., Babahmadi-Rezaei H. (2010). Oxidative damage to DNA and lipids: correlation with protein glycation in patients with type 1 diabetes. J. Clin. Lab. Anal. 24 72–76. 10.1002/jcla.20328
    1. Graham P., Pick L. (2017). Drosophila as a Model for diabetes and diseases of insulin resistance. Curr. Top. Dev. Biol 121 397–419. 10.1016/bs.ctdb.2016.07.011
    1. Gylling B., Myte R., Schneede J., Hallmans G., Haggstrom J., Johansson I., et al. (2017). Vitamin B-6 and colorectal cancer risk: a prospective population-based study using 3 distinct plasma markers of vitamin B-6 status. Am. J. Clin. Nutr. 105 897–904. 10.3945/ajcn.116.139337
    1. Hayakawa M., Shibata M. (1991). The in vitro and in vivo inhibition of protein glycosylation and diabetic vascular basement membrane thickening by pyridoxal-5′-phosphate. J. Nutr. Sci. Vitaminol. 37 149–159. 10.3177/jnsv.37.149
    1. Hellmann H., Mooney S. (2010). Vitamin B6: a molecule for human health? Molecules 15 442–459. 10.3390/molecules15010442
    1. Jain S. K. (2007). Vitamin B6 (pyridoxamine) supplementation and complications of diabetes. Metabolism 56 168–171. 10.1016/j.metabol.2006.09.002
    1. Kanellis P., Gagliardi M., Banath J. P., Szilard R. K., Nakada S., Galicia S., et al. (2007). A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions. PLoS Genet. 3:e134. 10.1371/journal.pgen.0030134
    1. Kasparek T. R., Humphrey T. C. (2011). DNA double-strand break repair pathways, chromosomal rearrangements and cancer. Semin. Cell Dev. Biol. 22 886–897. 10.1016/j.semcdb.2011.10.007
    1. Khanna K. K., Jackson S. P. (2001). DNA double-strand breaks: signaling, repair and the cancer connection. Nat. Genet. 27 247–254. 10.1038/85798
    1. Kotake Y., Ueda T., Mori T., Igaki S., Hattori M. (1975). Abnormal tryptophan metabolism and experimental diabetes by xanthurenic acid (XA). Acta Vitaminol. Enzymol. 29 236–239.
    1. Leklem J. E., Hollenbeck C. B. (1990). Acute ingestion of glucose decreases plasma pyridoxal 5′-phosphate and total vitamin B-6 concentration. Am. J. Clin. Nutr. 51 832–836. 10.1093/ajcn/51.5.832
    1. Liu Z., Li P., Zhao Z. H., Zhang Y., Ma Z. M., Wang S. X. (2016). Vitamin B6 prevents endothelial dysfunction, insulin resistance, and hepatic lipid accumulation in apoe (-/-) mice fed with high-fat diet. J. Diabetes Res. 2016:1748065. 10.1155/2016/1748065
    1. Marzio A., Merigliano C., Gatti M., Verni F. (2014). Sugar and chromosome stability: clastogenic effects of sugars in vitamin B6-deficient cells. PLoS Genet. 10:e1004199. 10.1371/journal.pgen.1004199
    1. McCormick D. B., Chen H. (1999). Update on interconversions of vitamin B-6 with its coenzyme. J. Nutr. 129 325–327. 10.1093/jn/129.2.325
    1. Mengoli V., Bucciarelli E., Lattao R., Piergentili R., Gatti M., Bonaccorsi S. (2014). The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure. PLoS Genet. 10:e1004739. 10.1371/journal.pgen.1004739
    1. Merigliano C., Marzio A., Renda F., Somma M. P., Gatti M., Verni F. (2017). A role for the twins protein phosphatase (PP2A-B55) in the maintenance of drosophila genome integrity. Genetics 205 1151–1167. 10.1534/genetics.116.192781
    1. Merigliano C., Mascolo E., La Torre M., Saggio I., Verni F. (2018). Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes. Sci. Rep. 8:11432. 10.1038/s41598-018-29801-z
    1. Mitelman F., Johansson B., Mertens F. (2007). The impact of translocations and gene fusions on cancer causation. Nat. Rev. Cancer 7 233–245. 10.1038/nrc2091
    1. Moreno-Navarrete J. M., Jove M., Ortega F., Xifra G., Ricart W., Obis E., et al. (2016). Metabolomics uncovers the role of adipose tissue PDXK in adipogenesis and systemic insulin sensitivity. Diabetologia 59 822–832. 10.1007/s00125-016-3863-1
    1. Musselman L. P., Fink J. L., Narzinski K., Ramachandran P. V., Hathiramani S. S., Cagan R. L., et al. (2011). A high-sugar diet produces obesity and insulin resistance in wild-type Drosophila. Dis. Model. Mech. 4 842–849. 10.1242/dmm.007948
    1. Nakamura S., Li H., Adijiang A., Pischetsrieder M., Niwa T. (2007). Pyridoxal phosphate prevents progression of diabetic nephropathy. Nephrol. Dial. Transplant. 22 2165–2174. 10.1093/ndt/gfm166
    1. Nix W. A., Zirwes R., Bangert V., Kaiser R. P., Schilling M., Hostalek U., et al. (2015). Vitamin B status in patients with type 2 diabetes mellitus with and without incipient nephropathy. Diabetes. Res. Clin. Pract. 107 157–165. 10.1016/j.diabres.2014.09.058
    1. Noto H., Tsujimoto T., Sasazuki T., Noda M. (2011). Significantly increased risk of cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Endocr. Pract. 17 616–628. 10.4158/EP10357.RA
    1. Okada M., Shibuya M., Yamamoto E., Murakami Y. (1999). Effect of diabetes on vitamin B6 requirement in experimental animals. Diabetes Obes. Metab. 1 221–225. 10.1046/j.1463-1326.1999.00028.x
    1. Oudes A. J., Herr C. M., Olsen Y., Fleming J. E. (1998). Age-dependent accumulation of advanced glycation end-products in adult Drosophila melanogaster. Mech. Ageing Dev. 100 221–229. 10.1016/S0047-6374(97)00146-2
    1. Oxenkrug G. (2013). Insulin resistance and dysregulation of tryptophan-kynurenine and kynurenine-nicotinamide adenine dinucleotide metabolic pathways. Mol. Neurobiol. 48 294–301. 10.1007/s12035-013-8497-4
    1. Percudani R., Peracchi A. (2003). A genomic overview of pyridoxal-phosphate-dependent enzymes. EMBO Rep. 4 850–854. 10.1038/sj.embor.embor914
    1. Rains J. L., Jain S. K. (2011). Oxidative stress, insulin signaling, and diabetes. Free Radic. Biol. Med. 50 567–575. 10.1016/j.freeradbiomed.2010.12.006
    1. Riminucci M., Saggio I., Robey P. G., Bianco P. (2006). Fibrous dysplasia as a stem cell disease. J. Bone Miner. Res. 21(Suppl. 2), 125–131. 10.1359/jbmr.06s224
    1. Rubi B. (2012). Pyridoxal 5’-phosphate (PLP) deficiency might contribute to the onset of type I diabetes. Med. Hypotheses 78 179–182. 10.1016/j.mehy.2011.10.021
    1. Sharma V., Collins L. B., Chen T., Herr N., Takeda S., Sun W., et al. (2016). Oxidative stress at low levels can induce clustered DNA lesions leading to NHEJ mediated mutations. Oncotarget 7 25377–25390. 10.18632/oncotarget.8298
    1. Shikata K., Ninomiya T., Kiyohara Y. (2013). Diabetes mellitus and cancer risk: review of the epidemiological evidence. Cancer Sci. 104 9–14. 10.1111/cas.12043
    1. Simao D., Pinto C., Fernandes P., Peddie C. J., Piersanti S., Collinson L. M., et al. (2016). Evaluation of helper-dependent canine adenovirus vectors in a 3D human CNS model. Gene Ther. 23 86–94. 10.1038/gt.2015.75
    1. Solomon L. R., Cohen K. (1989). Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus. Diabetes Metab. Res. Rev. 38 881–886.
    1. Spellacy W. N., Buhi W. C., Birk S. A. (1977). Vitamin B6 treatment of gestational diabetes mellitus: studies of blood glucose and plasma insulin. Am. J. Obstet. Gynecol. 127 599–602. 10.1016/0002-9378(77)90356-8
    1. Tatsch E., Bochi G. V., Piva S. J., De Carvalho J. A., Kober H., Torbitz V. D., et al. (2012). Association between DNA strand breakage and oxidative, inflammatory and endothelial biomarkers in type 2 diabetes. Mutat. Res. 732 16–20. 10.1016/j.mrfmmm.2012.01.004
    1. Thorpe S. R., Baynes J. W. (1996). Role of the Maillard reaction in diabetes mellitus and diseases of aging. Drugs Aging 9 69–77. 10.2165/00002512-199609020-00001
    1. Toyota T., Kai Y., Kakizaki M., Ohtsuka H., Shibata Y., Goto Y. (1981). The endocrine pancreas in pyridoxine deficient rats. Tohoku J. Exp. Med. 134 331–336. 10.1620/tjem.134.331
    1. Tsakiri E. N., Iliaki K. K., Hohn A., Grimm S., Papassideri I. S., Grune T., et al. (2013). Diet-derived advanced glycation end products or lipofuscin disrupts proteostasis and reduces life span in Drosophila melanogaster. Free Radic. Biol. Med. 65 1155–1163. 10.1016/j.freeradbiomed.2013.08.186
    1. Vigneri R. (2009). Diabetes: diabetes therapy and cancer risk. Nat. Rev. Endocrinol. 5 651–652. 10.1038/nrendo.2009.219
    1. Vlassara H., Palace M. R. (2002). Diabetes and advanced glycation endproducts. J. Intern. Med. 251 87–101. 10.1046/j.1365-2796.2002.00932.x
    1. Vlassara H., Uribarri J. (2014). Advanced glycation end products (AGE) and diabetes: cause, effect, or both? Curr. Diab. Rep. 14:453. 10.1007/s11892-013-0453-1

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