title: Effects of vitamin B6 metabolism on oncogenesis, tumor progression and therapeutic responses.
abstract: Pyridoxal-5'-phosphate (PLP), the bioactive form of vitamin B6, reportedly functions as a prosthetic group for >4% of classified enzymatic activities of the cell. It is therefore not surprising that alterations of vitamin B6 metabolism have been associated with multiple human diseases. As a striking example, mutations in the gene coding for antiquitin, an evolutionary old aldehyde dehydrogenase, result in pyridoxine-dependent seizures, owing to the accumulation of a metabolic intermediate that inactivates PLP. In addition, PLP is required for the catabolism of homocysteine by transsulfuration. Hence, reduced circulating levels of B6 vitamers (including PLP as well as its major precursor pyridoxine) are frequently paralleled by hyperhomocysteinemia, a condition that has been associated with an increased risk for multiple cardiovascular diseases. During the past 30 years, an intense wave of clinical investigation has attempted to dissect the putative links between vitamin B6 and cancer. Thus, high circulating levels of vitamin B6, as such or as they reflected reduced amounts of circulating homocysteine, have been associated with improved disease outcome in patients bearing a wide range of hematological and solid neoplasms. More recently, the proficiency of vitamin B6 metabolism has been shown to modulate the adaptive response of tumor cells to a plethora of physical and chemical stress conditions. Moreover, elevated levels of pyridoxal kinase (PDXK), the enzyme that converts pyridoxine and other vitamin B6 precursors into PLP, have been shown to constitute a good, therapy-independent prognostic marker in patients affected by non-small cell lung carcinoma (NSCLC). Here, we will discuss the clinical relevance of vitamin B6 metabolism as a prognostic factor in cancer patients.
authors: 1] Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France [2] Institut Gustave Roussy, Villejuif, France.
authors: L
authors: L
authors: Galluzzi
authors: E
authors: E
authors: Vacchelli
authors: J
authors: J
authors: Michels
authors: P
authors: P
authors: Garcia
authors: O
authors: O
authors: Kepp
authors: L
authors: L
authors: Senovilla
authors: I
authors: I
authors: Vitale
authors: G
authors: G
authors: Kroemer
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D063646:Carcinogenesis / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy*; D011379:Prognosis; D011731:Pyridoxal Kinase / Q000235:genetics / Q000378:metabolism; D011732:Pyridoxal Phosphate / Q000378:metabolism; D025101:Vitamin B 6 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D011732:Pyridoxal Phosphate; D025101:Vitamin B 6; D011731:Pyridoxal Kinase