Effect of pyridoxine and pyridoxal on the in vitro growth of human and murine cancer cells

Previous work conducted in our laboratories, using a murine model, suggested that the consumption of high levels of vitamin B-6 [pyridoxine (PN)] may suppress tumor development either by immune enhancement or by pyridoxal 5′-phosphate (PLP) growth regulation. To explore this relationship further, we assessed the effects of PN and pyridoxal (PL) on the growth of human (MCF-7, mammary; DU-145, prostate; CAKI-1, renal) and mouse (H238, fibrosarcoma) cancer cell lines. The incubation of cancer cells for 3 (H238) to 20 (MCF-7, DU-145, CAKI-1) days in culture media supplemented with high doses of PN (2.5-5.0 mM) or PL (0.05-5.0 mM) showed significant reductions in proliferation (13% to 100%) as compared to control cultures. PL was more efficacious than PN as a cytotoxin. Cell mortality was observed in a dose-dependent manner, but sensitivity to PN and PL at concentrations approximating physiologic levels (0.005 mM) did not retard growth. Intracellular levels of PL and PLP were significantly elevated in H238 cultures exposed to pharmacologic, but not physiologic concentrations of PN and PL. MCF-7, DU-145, CAKI-1, and H238 cells cultured for 3 h in media supplemented with 0.5 mM PL and labeled with [³H] precursors generally incorporated significantly less leucine, uridine, and thymidine into TCA-precipitable material than did control cultures. In contrast, cells supplemented with 0.005 mM PL showed no inhibition in incorporation. The results indicate that physiological concentrations of PN and PL may not be directly cytotoxic to human or animal cancer cells in vivo.