Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer

Abstract

Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.

EGFR inhibitors exacerbate differentiation and cell cycle arrest induced by retinoic acid and vitamin D3in acute myeloid leukemia cells

“…63,64 Briefly, cells were lysed on ice in a buffer containing 1% NP40, 20 mM HEPES pH 7.9, 10 mM KCl, 1 mM EDTA, 10% glycerol, 1 mM orthovanadate, 1 mM PMSF, 1 mM dithiothreitol, and 10 µg/mL aprotinin, leupeptin, pepstatin. Data treatment and statistical analyses Unless otherwise specified, all experiments were performed in triplicate parallel instances and independently repeated at least 2 times.…”

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

“…The majority of circulating vitamin B12 is bound to HC (70-90%); however, it is considered to be biologically unavailable to most cells. The remaining 10-30% of vitamin B12 is bound to holotranscobalamin (holo TC), which delivers the vitamin into metabolising cells from its site of absorption [71,72]. The measurement of holo TC has been found to be more diagnostically accurate for detecting early vitamin B12 deficiency compared to total serum vitamin B12, which measures both HC and TC levels [63].…”

“…The general consensus was that vitamin B6 exerted anti-neoplastic activity. In 2012, vitamin B6 was reported to exhibit a synergistic effect with certain chemotherapeutic drugs [72]. Small participant number clinical studies were then conducted and subsequently expanded.…”

“…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].…”

“…From the studies discussed, it would be adventitious for people with cancer to take a low dose supplement of vitamin B6, approximately 40 mg daily. Interactions with chemotherapeutic agents still require further investigation with studies showing beneficial effects when administered in conjunction with cisplatin [72]. However, considering that B6 has affected dose response when given in high doses, further studies assessing dose still need to be completed [78].…”