Curcumin binds tubulin, induces mitotic catastrophe, and impedes normal endothelial cell proliferation
Curcumin binds tubulin, induces mitotic catastrophe, and impedes normal endothelial cell proliferation
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DOI：
10.1016/j.fct.2013.08.008
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发表时间：
2013-10-01
影响因子：
4.3
通讯作者：
Young, Andrew J.
中科院分区：
文献类型：
--
作者：
Jackson, Steven J. T.;Murphy, Laura L.;Young, Andrew J.
姜黄素是姜黄香料的一种成分，赋予咖喱风味和颜色，被认为在生物组织中具有抗炎和抗氧化特性。然而，虽然这种功效已经在致癌作用的背景下进行了描述，但姜黄素对正常细胞周期调控的影响却知之甚少。在这里，我们提供了姜黄素在增殖的牛主动脉内皮细胞中的毒性的证据，其浓度与饮食相关，并且低于先前在癌症模型中报道的浓度。在证实姜黄素以剂量依赖性方式上调血红素加氧酶-1的能力后，我们发现最低有效姜黄素浓度也抑制内皮细胞DNA合成。此外，姜黄素浓度低于最低2 μ M的阈值需要诱导血红素加氧酶-1结合微管蛋白在体外和触发体内有丝分裂灾难的标志性证据。浓度低至0.1 μ M姜黄素导致不成比例的DNA分离，核碎裂，和微核在增殖的内皮细胞。虽然提出了生理姜黄素浓度抑制细胞周期进程的机制，但这些发现描述了迄今为止未被认识到的姜黄素毒性，对内皮生长、发育和组织愈合具有潜在影响。爱思唯尔有限公司出版
Curcumin, a component of turmeric spice that imparts flavor and color to curry, is thought to possess anti-inflammatory and antioxidant properties in biological tissues. However, while such efficacies have been described in the context of carcinogenesis, the impact of curcumin on normal cell cycle regulation is poorly understood. Here, we provide evidence of curcumin toxicity in proliferating bovine aortic endothelial cells, at concentrations relevant to the diet and below those previously reported in cancer models. Upon confirming curcumin's ability to upregulate hemeoxygenase-1 in a dose-dependent fashion, we found the minimally efficacious curcumin concentration to also inhibit endothelial cell DNA synthesis. Moreover, curcumin concentrations below the minimum 2 mu M threshold required to induce hemeoxygenase-1 bound tubulin protein in vitro and triggered hallmark evidence of mitotic catastrophe in vivo. Concentrations as low as 0.1 mu M curcumin led to disproportionate DNA segregation, karyorrhexis, and micronucleation in proliferating endothelial cells. While suggesting a mechanism by which physiological curcumin concentrations inhibit cell cycle progression, these findings describe heretofore unappreciated curcumin toxicity with potential implications for endothelial growth, development, and tissue healing. Published by Elsevier Ltd.