Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Mutat Res. 2010 Jun 1;688(1-2):72-7. doi: 10.1016/j.mrfmmm.2010.03.011. Epub 2010 Apr 2.
Curcumin is a natural compound that has been extensively observed due to its potential as an anticancer drug. Curcumin restrains cancer cell progression via telomerase activity suppression. However, the exact mechanism is still unknown. In this study, we demonstrate that the effects of curcumin on cell viability and telomerase activity can be blunted by reactive oxygen species (ROS) inhibitor N-acetyl cysteine (NAC). The ROS induced by curcumin in A549 cells was detected by flow cytometry. Using Western blot and RT-PCR, human telomerase reverse transcriptase (hTERT) decreased in the presence of curcumin. Sp1 is one of the important transcription factors in hTERT expression. Our data showed that curcumin decreases the expression of Sp1 through proteasome pathway. In addition, NAC blunted the Sp1 reduction and hTERT downregulation by curcumin. Further, reporter assay and DNA affinity precipitation assay confirmed the influence of curcumin on Sp1 in hTERT regulation. This is the first study to demonstrate that curcumin induces ROS production resulting in Sp1 binding activity inhibition and hTERT downregulation.
姜黄素是一种天然化合物,由于其作为抗癌药物的潜力而受到广泛关注。姜黄素通过抑制端粒酶活性来抑制癌细胞的进展。然而,其确切的机制尚不清楚。在这项研究中,我们证明了活性氧(ROS)抑制剂 N-乙酰半胱氨酸(NAC)可以减弱姜黄素对细胞活力和端粒酶活性的影响。通过流式细胞术检测姜黄素在 A549 细胞中诱导的 ROS。使用 Western blot 和 RT-PCR,发现姜黄素存在时人端粒酶逆转录酶(hTERT)减少。Sp1 是 hTERT 表达的重要转录因子之一。我们的数据表明,姜黄素通过蛋白酶体途径降低 Sp1 的表达。此外,NAC 减弱了姜黄素引起的 Sp1 减少和 hTERT 下调。进一步的报告基因检测和 DNA 亲和沉淀检测证实了姜黄素对 Sp1 在 hTERT 调节中的影响。这是第一项研究表明,姜黄素诱导 ROS 产生,导致 Sp1 结合活性抑制和 hTERT 下调。