Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 824, Taiwan.
J Nutr Biochem. 2011 Jan;22(1):46-52. doi: 10.1016/j.jnutbio.2009.11.010. Epub 2010 Mar 20.
Nucleophosmin (NPM/B23) is a nucleolar phosphoprotein involved in cellular response to many different stimuli. Herein, we studied the molecular mechanism of NPM/B23 induction by curcumin, a natural AP-1 inhibitor with antitumor properties. Exposure to 5-30 μM curcumin significantly and dose-dependently increased the level of NPM/B23 in non-transformed NIH 3T3 cells but not HeLa cells and F9 cells. Besides, the transformed F9 and HeLa cells are more sensitive to curcumin-induced cell death and growth inhibition than NIH 3T3 cells. Overexpression of c-Jun, but not c-Fos, decreased ∼40% of NPM/B23 and enhanced the sensitivity of NIH 3T3 cells to 30 μM curcumin. Furthermore, down-regulation of NPM/B23 by transfection with NPM/B23 antisense plasmid enhanced the sensitivity to curcumin-induced cell death and growth inhibition. These results indicated that NPM/B23 expression regulates cellular sensitivity to curcumin. Besides, NPM/B23 knockdown may facilitate as a novel strategy to promote the sensitivity of cancer cells to curcumin.
核仁磷酸蛋白(NPM/B23)是一种参与细胞对多种不同刺激物反应的核仁磷酸蛋白。在此,我们研究了姜黄素(一种具有抗肿瘤特性的天然 AP-1 抑制剂)诱导 NPM/B23 的分子机制。暴露于 5-30 μM 姜黄素可显著且剂量依赖性地增加非转化 NIH 3T3 细胞而非 HeLa 细胞和 F9 细胞中 NPM/B23 的水平。此外,转化的 F9 和 HeLa 细胞对姜黄素诱导的细胞死亡和生长抑制比 NIH 3T3 细胞更为敏感。过表达 c-Jun,但不是 c-Fos,可使 NPM/B23 减少约 40%,并增强 NIH 3T3 细胞对 30 μM 姜黄素的敏感性。此外,用 NPM/B23 反义质粒转染下调 NPM/B23 可增强对姜黄素诱导的细胞死亡和生长抑制的敏感性。这些结果表明 NPM/B23 表达调节细胞对姜黄素的敏感性。此外,NPM/B23 敲低可能有助于促进癌细胞对姜黄素的敏感性。