Jiao Yan, Wilkinson John, Christine Pietsch E, Buss Joan L, Wang Wei, Planalp Roy, Torti Frank M, Torti Suzy V
Department of Cancer Biology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
Free Radic Biol Med. 2006 Apr 1;40(7):1152-60. doi: 10.1016/j.freeradbiomed.2005.11.003.
Curcumin is among the more successful chemopreventive compounds investigated in recent years, and is currently in human trials to prevent cancer. The mechanism of action of curcumin is complex and likely multifactorial. We have made the unexpected observation that curcumin strikingly modulates proteins of iron metabolism in cells and in tissues, suggesting that curcumin has properties of an iron chelator. Curcumin increased mRNA levels of ferritin and GSTalpha in cultured liver cells. Unexpectedly, however, although levels of GSTalpha protein increased in parallel with mRNA levels in response to curcumin, levels of ferritin protein declined. Since iron chelators repress ferritin translation, we considered that curcumin may act as an iron chelator. To test this hypothesis, we measured the effect of curcumin on transferrin receptor 1, a protein stabilized under conditions of iron limitation, as well as the ability of curcumin to activate iron regulatory proteins (IRPs). Both transferrin receptor 1 and activated IRP, indicators of iron depletion, increased in response to curcumin. Consistent with the hypothesis that curcumin acts as an iron chelator, mice that were fed diets supplemented with curcumin exhibited a decline in levels of ferritin protein in the liver. These results suggest that iron chelation may be an additional mode of action of curcumin.
姜黄素是近年来研究较为成功的化学预防化合物之一，目前正处于预防癌症的人体试验阶段。姜黄素的作用机制复杂，可能是多因素的。我们有一个意外的发现，即姜黄素能显著调节细胞和组织中铁代谢的蛋白质，这表明姜黄素具有铁螯合剂的特性。姜黄素可提高培养的肝细胞中铁蛋白和谷胱甘肽S-转移酶α（GSTalpha）的mRNA水平。然而，出乎意料的是，尽管GSTalpha蛋白水平随着姜黄素处理后mRNA水平的升高而平行增加，但铁蛋白水平却下降了。由于铁螯合剂会抑制铁蛋白的翻译，我们认为姜黄素可能作为一种铁螯合剂发挥作用。为了验证这一假设，我们检测了姜黄素对转铁蛋白受体1的影响，转铁蛋白受体1是一种在铁限制条件下稳定的蛋白质，同时还检测了姜黄素激活铁调节蛋白（IRPs）的能力。转铁蛋白受体1和激活的IRP，作为铁缺乏的指标，在姜黄素处理后均增加。与姜黄素作为铁螯合剂发挥作用的假设一致，喂食添加姜黄素饮食的小鼠肝脏中铁蛋白水平下降。这些结果表明，铁螯合可能是姜黄素的另一种作用方式。
