Identification of potential pathways involved in the induction of cell cycle arrest and apoptosis by a new 4-arylidene curcumin analogue T63 in lung cancer cells: a comparative proteomic analysis
Identification of potential pathways involved in the induction of cell cycle arrest and apoptosis by a new 4-arylidene curcumin analogue T63 in lung cancer cells: a comparative proteomic analysis
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肺癌细胞中新型 4-亚芳基姜黄素类似物 T63 诱导细胞周期停滞和细胞凋亡的潜在途径的鉴定：比较蛋白质组学分析
DOI：
10.1039/c3mb70553f
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发表时间：
2014-01-01
影响因子：
--
通讯作者：
Du, Jun
中科院分区：
文献类型：
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作者：
Liu, Hao;Liu, Yan-Zhen;Du, Jun
姜黄素（Curcumin，Diferuloylmethane）是姜黄（Curcumalonga）中的一种多酚类天然产物，具有多种抗肿瘤活性。然而，姜黄素的临床应用仍然受到限制，由于其不良的药代动力学特性。因此，开发具有增强抗癌活性的姜黄素结构类似物至关重要。T63是我们前期合成的一种新型4-亚芳基姜黄素类似物，其体内外抗肿瘤活性均高于姜黄素。然而，其抗肿瘤作用的确切分子机制尚未得到很好的阐明。利用双向凝胶电泳（2-DE）为基础的蛋白质组学方法，我们确定了66个差异表达的蛋白质。与姜黄素类似，T63显示出多种分子靶标。我们认为T63诱导的细胞周期阻滞和细胞凋亡可能与ROS产生和线粒体功能障碍、蛋白酶体、HSP 90和14-3-3蛋白的抑制有关。这些结果表明，姜黄素类似物T63具有诱导细胞周期阻滞和凋亡的作用，是一种有效的抗肿瘤药物，为进一步研究T63的抗肿瘤作用及其分子机制提供了宝贵的资源。
Curcumin (diferuloylmethane) is a polyphenol natural product of the plant Curcuma longa, and has a diversity of antitumor activities. However, the clinical application of curcumin remains limited due to its poor pharmacokinetic characteristics. It is therefore critical to develop structural analogues of curcumin with increasing anticancer activity. T63, a new 4-arylidene curcumin analogue, was synthesized in our previous studies and exhibited higher in vitro and in vivo anti-tumor activities compared to curcumin. However, the precise molecular mechanism of its anti-tumor effects has not been well elucidated. Using a two-dimensional gel electrophoresis (2-DE)-based proteomic approach, we identified 66 differentially expressed proteins. Similarly to curcumin, T63 showed a diverse range of molecular targets. We proposed that induction of ROS generation and mitochondrial dysfunction, inhibition of proteasome, HSP90, and 14-3-3 proteins play important roles in T63-induced cell cycle arrest and apoptosis. These data indicate that the novel curcumin analogue T63 is a potent anti-tumor agent, which can induce cell cycle arrest and apoptosis, and also provided valuable resources for further study of the anti-tumor effects and molecular mechanisms of T63.