Matsubara Kiminori, Matsumoto Hiroaki, Mizushina Yoshiyuki, Lee Jung Sup, Kato Norihisa
Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, Okayama 719-119, Japan.
Int J Mol Med. 2003 Jul;12(1):51-5.
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.
最近，在使用大鼠主动脉环的体外无血清基质培养模型中证实了磷酸吡哆醛（PLP）和吡哆醛（PL）的抗血管生成作用。为了阐明维生素B6如何抑制血管生成，本研究旨在检测其对人脐静脉内皮细胞（HUVEC）增殖和HUVEC管形成的影响。与体外血管生成试验的结果一致，250微摩尔的PLP和PL显著抑制了HUVEC的增殖，而吡哆醇（PN）和吡哆胺（PM）在此浓度下无活性。在50-250微摩尔范围内，PLP和PL对HUVEC增殖的抑制呈明显的剂量依赖性。然而，PLP和PL对HUVEC管形成没有影响。PLP还抑制了复制性DNA聚合酶以及DNA拓扑异构酶I和II的活性。这些结果表明，维生素B6至少部分通过抑制DNA聚合酶和DNA拓扑异构酶来抑制内皮细胞增殖和血管生成。
