Chen Jianping, Li Lin, Su Jianyu, Li Bing, Zhang Xia, Chen Tianfeng
†College of Light Industry and Food Sciences, South China University of Technology, Guangzhou 510640, China.
§College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China.
J Agric Food Chem. 2015 Jul 22;63(28):6440-9. doi: 10.1021/acs.jafc.5b01773. Epub 2015 Jul 8.
Curcumin (Cur), an active ingredient from the rhizome of the plant Curcuma longa, has wide anticancer activities. However, due to its poor solubility and hence poor absorption, Cur has limited clinical applications. It is therefore important to develop an effective method to improve its absorption. Natural borneol (NB), a terpene and bicyclic organic compound, has been extensively used as a food additive, and our previous studies show that it can improve the uptake of Cur in cancer cells. However, the anticancer mechanism of NB/Cur remains unclear. In this study, the effects of NB/Cur on HepG2 cells were investigated by proteomic analysis. The results showed that 32 differentially expressed proteins identified by matrix assisted laser desorption ionization time-of-flight mass spectrometry were significantly changed after NB/Cur treated HepG2 cells for 24 h. Moreover, 17 proteins increased and 12 proteins decreased significantly. Biological progress categorization demonstrated that the identified proteins were mainly associated with cell cycle and apoptosis (28.1%). Subcellular location categorization exhibited that the identified proteins were mainly located in nucleus (28.1%) and mitochondrion (21.9%). Among of all proteins, we selected three differential proteins (hnRNPC1/C2, NPM, and PSMA5), which were associated with the p53 pathway. Down-regulation of hnRNPC1/C2 and NPM contributed to the enhancement of phosphorylated p53. Activated p53 and down-regulation of PSMA5 resulted in an increase in p21 protein. Further studies showed that NB/Cur induced reactive oxygen species (ROS) generation, indicating that ROS might be upstream of the G2/M arrest signaling pathway. In summary, the results exhibited the whole proteomic response of HepG2 cells to NB/Cur, which might lead to a better understanding of its underlying anticancer mechanisms.
姜黄素（Cur）是植物姜黄根茎中的一种活性成分，具有广泛的抗癌活性。然而，由于其溶解性差，吸收也差，Cur的临床应用有限。因此，开发一种有效的方法来提高其吸收非常重要。天然冰片（NB）是一种萜类双环有机化合物，已被广泛用作食品添加剂，我们之前的研究表明它可以提高癌细胞对Cur的摄取。然而，NB/Cur的抗癌机制仍不清楚。在本研究中，通过蛋白质组学分析研究了NB/Cur对HepG2细胞的影响。结果表明，基质辅助激光解吸电离飞行时间质谱鉴定出的32种差异表达蛋白在NB/Cur处理HepG2细胞24小时后发生了显著变化。此外，17种蛋白显著增加，12种蛋白显著减少。生物学进程分类表明，鉴定出的蛋白主要与细胞周期和凋亡相关（28.1%）。亚细胞定位分类显示，鉴定出的蛋白主要位于细胞核（28.1%）和线粒体（21.9%）。在所有蛋白中，我们选择了三种与p53通路相关的差异蛋白（hnRNPC1/C2、NPM和PSMA5）。hnRNPC1/C2和NPM的下调有助于磷酸化p53的增强。活化的p53和PSMA5的下调导致p21蛋白增加。进一步的研究表明，NB/Cur诱导活性氧（ROS）生成，表明ROS可能是G2/M期阻滞信号通路的上游。总之，结果展示了HepG2细胞对NB/Cur的整体蛋白质组反应，这可能有助于更好地理解其潜在的抗癌机制。
