Evaluation of cancer patient leukocyte responses in the presence of physiologic and pharmacologic pyridoxine and pyridoxal levels

Abstract

Peripheral blood samples from six cancer patients (five colon cancer, one lung cancer) and six healthy volunteers were tested in vitro for oxygen radical production by phagocytic cells and in assays of mitogen-induced lymphoblastogenesis at physiologic and pharmacologic concentrations of pyridoxine (PN, 1.8-96 nmol/ml) or pyridoxal (PL, 0.08-90 nmol/ml). Plasma levels of pyridoxal-5'-phosphate (PLP), 4-pyridoxic acid (4PA), pyridoxamine phosphate (PMP), and PL were also determined. Phagocytic cells from three patients showed significantly increased capacity for oxygen radical production when incubated in PL-, but not PN-supplemented media. Oxygen burst capacity of cells from healthy subjects was significantly enhanced by PN-, but not PL-enriched media. Lymphocyte responsiveness to phytohemagglutinin or pokeweed mitogen (PWM) stimulation showed a modest increase in cell activation in three patients as the concentration of PN was increased; with concanavalin A, two showed enhanced responsiveness. On the other hand, PL-supplementation resulted in greater cell proliferation only with PWM. The cancer patients had significantly lower plasma PLP, 4PA, and PMP levels when compared with the healthy volunteers. These data indicate that in the cancer patients and in a majority of the healthy volunteers, vitamin B-6 status was marginal or deficient and suggest that increasing PN or PL in vivo levels may augment functions related to cell-mediated immunity.

Pyridoxal Phosphate Inhibits Pituitary Cell Proliferation and Hormone Secretion

“…This study demonstrates that pharmacological doses of pyridoxal phosphate, the biologically active form of vitamin B6, inhibits rodent pituitary tumor cell proliferation, consistent with literature reports of pyridoxine-induced anti-proliferative effects on other tumor cells (4)(5)(6)(7)(8)(9)(10)(11)(12). This effect was not caused by necrosis or potential toxic action of pyridoxine at high doses, because cell numbers were not significantly changed at the end of 7 days of exposure to 1 mM PLP, and cell growth recovered to normal levels after PLP withdrawal.…”

“…Dietary supplemental pyridoxine (7 or > 7 mg/kg body weight) significantly reduced colon tumorigenesis and cell proliferation in mice receiving azoxymethane (47,48), and highfat diet markedly enhances pyridoxine-induced inhibitory effect (49). In human studies, there is an association between cancer incidence and lower plasma PLP levels (4)(5)(6)(7)(8). These results suggest that pyridoxine doses required to inhibit tumor cell growth in vivo are much lower than those required in vitro.…”

“…Patients with breast (4), or colon (5,6), bladder (7), or laryngeal (8) cancers, and or Hodgkin's disease (1) have lower plasma PLP levels compared with healthy controls. In vitro studies have shown that pharmacologic doses of vitamin B6 (from 0.25 to 5 mM) inhibit cell proliferation and protein synthesis in HepG2 human hepatoma cells (9), human malignant melanoma (10,11), and human lymphocytes (12).…”