Pan Wei, Yang Hui, Cao Cong, Song Xiuzu, Wallin Brittany, Kivlin Rebecca, Lu Shan, Hu Gang, Di Wen, Wan Yinsheng
Department of Biology, Providence College, Providence, RI 02908, USA.
Oncol Rep. 2008 Dec;20(6):1553-9.
AMP-activated protein kinase (AMPK), an evolutionarily conserved serine/threonine protein kinase, serves as an energy sensor in all eukaryotic cells. Recent findings suggest that AMPK activation strongly suppresses cell proliferation and induces cell apoptosis in a variety of cancer cells. Our study demonstrated that chemopreventive agent curcumin strongly activates AMPK in a p38-dependent manner in CaOV3 ovarian cancer cells. Pretreatment of cells with compound C (AMPK inhibitor) and SB203580 (p38 inhibitor) attenuates curcumin-induced cell death. We also observed that curcumin induces p53 phosphorylation (Ser 15) and both compound C and SB203580 pretreatment inhibit p53 phosphorylation. Collectively, our data suggest that AMPK is a new molecular target of curcumin and AMPK activation partially contributes to the cytotoxic effect of curcumin in ovarian cancer cells.
AMP激活的蛋白激酶（AMPK）是一种进化上保守的丝氨酸/苏氨酸蛋白激酶，在所有真核细胞中作为能量传感器。最近的研究结果表明，AMPK激活强烈抑制多种癌细胞的细胞增殖并诱导细胞凋亡。我们的研究表明，化学预防剂姜黄素在CaOV3卵巢癌细胞中以p38依赖的方式强烈激活AMPK。用化合物C（AMPK抑制剂）和SB203580（p38抑制剂）预处理细胞可减弱姜黄素诱导的细胞死亡。我们还观察到姜黄素诱导p53磷酸化（Ser 15），而化合物C和SB203580预处理均抑制p53磷酸化。总体而言，我们的数据表明AMPK是姜黄素的一个新分子靶点，AMPK激活部分有助于姜黄素对卵巢癌细胞的细胞毒性作用。
