The multifaceted role of vitamin B6 in cancer: Drosophila as a model system to investigate DNA damage

Abstract

A perturbed uptake of micronutrients, such as minerals and vitamins, impacts on different human diseases, including cancer and neurological disorders. Several data converge towards a crucial role played by many micronutrients in genome integrity maintenance and in the establishment of a correct DNA methylation pattern. Failure in the proper accomplishment of these processes accelerates senescence and increases the risk of developing cancer, by promoting the formation of chromosome aberrations and deregulating the expression of oncogenes. Here, the main recent evidence regarding the impact of some B vitamins on DNA damage and cancer is summarized, providing an integrated and updated analysis, mainly centred on vitamin B₆. In many cases, it is difficult to finely predict the optimal vitamin rate that is able to protect against DNA damage, as this can be influenced by a given individual's genotype. For this purpose, a precious resort is represented by model organisms which allow limitations imposed by more complex systems to be overcome. In this review, we show that Drosophila can be a useful model to deeply understand mechanisms underlying the relationship between vitamin B₆ and genome integrity.

Keywords: Drosophila melanogaster; cancer; genome integrity; vitamin B6.

Figure 1.

Schematic of B₉ metabolism comprising the thymidylate cycle (red diagram), the methionine cycle (green diagram) and the purine biosynthesis pathway (blue diagram). The enzymes involved are: dihydrofolate reductase (DHFR); thymidylate synthase (TS); serine hydroxymethyltransferase (SHMT); methylenetetrahydrofolate reductase (MTHFR); methionine synthase (MS); methionine adenosyltransferases (MAT); S-adenosylhomocysteinase (SHase); glycine cleavage system (GCS); methylenetetrahydrofolate dehydrogenase (MTHFD); 10-formyltetrahydrofolate dehydrogenase (FDH); formyltetrahydrofolate synthetase (FTHFS).

Figure 2.

Schematic of vitamin B₆ metabolism in humans. The orange diagram corresponds to the pyridoxal 5′-phosphate salvage pathway. PLP, pyridoxal 5'-phosphate; PNP, pyridoxine 5'-phosphate; PMP, pyridoxamine 5'-phosphate; PL, pyridoxal; PN, pyridoxine; PM, pyridoxamine; PA, 4-pyridoxic acid; PDXK: pyridoxal kinase; TNSALP: tissue-non-specific alkaline phosphatases; PLPP, pyridoxal 5'-phosphate phosphatase; ALDH, aldehyde dehydrogenases; POX, pyridoxal oxidase; AOX, aldehyde oxidases.

Figure 3.

Relationships between vitamin B₆ and cancer. In the scheme, green arrows represent a protective effect against cancer, whereas red arrows indicate a promoting cancer effect.

Figure 4.

Effects of vitamin B₆ deficiency inferred from studies carried out in Drosophila.