title: Proteomic Analysis of G2/M Arrest Triggered by Natural Borneol/Curcumin in HepG2 Cells, the Importance of the Reactive Oxygen Species-p53 Pathway.
abstract: 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.
authors.affiliation: †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.
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
authors.affiliation: †College of Light Industry and Food Sciences, South China University of Technology, Guangzhou 510640, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: †College of Light Industry and Food Sciences, South China University of Technology, Guangzhou 510640, China.|#Guangdong Hua Qing Yuan Biological Technology Co., Ltd., Meizhou, 514600, China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Su
authors.affiliation: †College of Light Industry and Food Sciences, South China University of Technology, Guangzhou 510640, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: †College of Light Industry and Food Sciences, South China University of Technology, Guangzhou 510640, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: ‡Department of Chemistry, Jinan University, Guangzhou, 510632, China.|#Guangdong Hua Qing Yuan Biological Technology Co., Ltd., Meizhou, 514600, China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents; D017209:Apoptosis; D001892:Camphanes / Q000494:pharmacology*; D002453:Cell Cycle; D003474:Curcumin / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001892:Camphanes; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D003474:Curcumin; C022871:isoborneol
keywords: G2/M phase; ROS-p53 pathway; curcumin; natural borneol; proteomics