Pro-angiogenesis action of arsenic and its reversal by selenium-derived compounds (Retracted Article)
Pro-angiogenesis action of arsenic and its reversal by selenium-derived compounds (Retracted Article)
复制标题
DOI：
10.1093/carcin/bgl229
复制
发表时间：
2007-05-01
期刊：
影响因子：
4.7
通讯作者：
Block, Eric
中科院分区：
文献类型：
--
作者：
Mousa, Shaker A.;O'Connor, Laura;Block, Eric
饮用水中的无机砷（亚砷酸盐和砷酸盐）与皮肤癌和心血管疾病发病率增加有关。此外，研究已经证明亚砷酸盐的促血管生成作用及其对肿瘤血管生成和肿瘤进展的潜在促进作用。此外，最近的报告表明，逆转的皮肤共致癌作用的有机硒化合物。本研究旨在探讨低浓度砷对血管生成的影响及其机制，以及不同硒衍生物对砷血管生成的逆转作用。用鸡胚绒毛尿囊膜（CAM）模型测定了亚砷酸钠的促血管生成作用和机制，并与标准促血管生成因子如碱性成纤维细胞生长因子（b-FGF）进行了比较。此外，还在CAM模型中确定了各种硒衍生化合物（如二甲基硒酮、二苯基硒酮、亚硒酸钠或Se-甲基硒代半胱氨酸）在逆转亚砷酸盐或b-FGF的促血管生成作用中的潜在作用。二甲基硒酮、二苯硒酮、亚硒酸钠和硒甲基硒代半胱氨酸均能显著阻断亚砷酸钠和b-FGF的促血管生成作用（P < 0.01）。细胞外信号调节激酶1和2（ERK 1/2）激活抑制剂PD 98059阻断了33 nM亚砷酸钠或b-FGF的促血管生成作用（P < 0.01）。此外，砷或b-FGF的促血管生成作用也被α v β 3拮抗剂XT 199阻断（P < 0.01）。这些数据表明，砷的促血管生成作用起始于质膜整合素α v β 3，涉及ERK 1/2通路的激活，并被各种硒衍生化合物有效逆转。
Inorganic arsenic (arsenite and arsenate) in drinking water has been associated with skin cancers and increased incidence of cardiovascular diseases. Additionally, studies have demonstrated the pro-angiogenic effect of arsenite and its potential promotion of tumor angiogenesis and tumor progression. Furthermore, recent reports demonstrated reversal of skin co-carcinogenesis by an organoselenium compound. The present study was undertaken to determine the effect and mechanism on angiogenesis of arsenite at low level and its potential reversal by various selenium-derived compounds. The pro-angiogenesis effects and mechanisms of sodium arsenite were determined using the chick chorioallantoic membrane (CAM) model over 3 days and compared with standard pro-angiogenesis factors, such as basic fibroblast growth factor (b-FGF). Additionally, the potential effect of various selenium-derived compounds-such as dimethyl selenone, diphenyl selenone, sodium selenite or Se-methyl selenocysteine-in reversing the pro-angiogenesis effect of arsenite or b-FGF was also determined in the CAM model. The pro-angiogenesis effect of arsenite or b-FGF was significantly (P < 0.01) blocked by dimethyl selenone, diphenyl selenone, sodium selenite or Se-methyl selenocysteine. The pro-angiogenesis effect of either sodium arsenite at 33 nM or b-FGF was blocked (P < 0.01) by the extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation inhibitor, PD 98059. Additionally, the pro-angiogenic effect of arsenic or b-FGF was blocked as well (P < 0.01) by the alpha v beta 3 antagonist, XT199. These data suggest that the pro-angiogenesis effect of arsenic is initiated at the plasma membrane integrin alpha v beta 3, involves activation of the ERK1/2 pathway and is effectively reversed by various selenium-derived compounds.