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.

A pilot clinical trial assessing the efficacy and safety of supplementation with a B complex vitamin to reduce the incidence of chemotherapy induced peripheral neuropathy in patients diagnosed with a malignancy

“…There have been a number of well-established relationships identified between vitamin B6 and cancer; these include that a proficient metabolism of vitamin B6 is required to sustain the anabolic requirements of highly proliferating cells, such as tumour cells and the immune system [72,74]. This assists in understanding why cancer patients can potentially suffer from a vitamin B6 deficiency and, furthermore, that cancer-associated immunosuppression may partially be derived from a vitamin B6 deficiency [69].…”

“…Vitamin B6 investigations began around 1950 with researchers looking at the influence of vitamin B6 on oncogenesis and tumour progression [69]. The majority of these initial studies included in vitro and animal studies on immune-deficient rodents.…”

“…The use of a B complex supplement in cancer has been limited in human trials, although epidemiologic studies suggest cancer patients are regularly administering these supplements [71]. Both vitamin B6 and folate have had numerous studies conducted in vitro and in animal models with less studies conducted on humans [69]. There have also been safety issues that have been brought to the forefront concerning supplementation or fortification [70].…”

“…In addition, researchers also found that elevated circulating amounts of B6 vitamers in addition to high consumption of vitamin B6 correlated with a reduced incidence of several cancers. Furthermore, a high intra-tumoral expression level of pyridoxal kinase (PDXK -the enzyme that converts all forms of vitamin B6 to PLP) was reported to possibly improve disease outcome among lung cancer patients (NSCLC) [69].…”

“…Moreover, the role of vitamin supplementation in those diagnosed with cancer is still unclear. The two main B vitamins researched for cancer are folic acid and vitamin B6 [69,70]. The use of a B complex supplement in cancer has been limited in human trials, although epidemiologic studies suggest cancer patients are regularly administering these supplements [71].…”