Inhibitory effect of pyridoxal 5'-phosphate on endothelial cell proliferation, replicative DNA polymerase and DNA topoisomerase.

Recently, the anti-angiogenic effect of pyridoxal 5'-phosphate (PLP) and pyridoxal (PL) was demonstrated in an ex vivo serum-free matrix culture model using rat aortic ring. To clarify how vitamin B6 inhibits angiogenesis, this study was performed to examine the effect on human umbilical vein endothelial cell (HUVEC) proliferation and HUVEC tube formation. Consistent with the result on an ex vivo angiogenesis assay, PLP and PL at 250 microM markedly suppressed the proliferation of HUVEC, while pyridoxine (PN) and pyridoxamine (PM) were inactive at this concentration. Suppression in HUVEC proliferation by PLP and PL was evident in a dose-dependent manner within the range of 50-250 microM. However, the HUVEC tube formation was unaffected by PLP and PL. The activities of replicative DNA polymerase and DNA topoisomerases I and II were also inhibited by PLP. These results suggest that vitamin B6 suppresses endothelial cell proliferation and angiogenesis at least in part by inhibiting DNA polymerase and DNA topoisomerases.