title: 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.
abstract: 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.
authors.affiliation: Affiliated Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou 510095, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Yan-Zhen
authors.initials: YZ
authors.lastname: Liu
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Wang
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Bin-Hua
authors.initials: BH
authors.lastname: Zhou
authors.forename: Ying-Lin
authors.initials: YL
authors.lastname: Zuo
authors.forename: Shao-Hui
authors.initials: SH
authors.lastname: Cai
authors.forename: Xian-Zhang
authors.initials: XZ
authors.lastname: Bu
authors.forename: Jun
authors.initials: J
authors.lastname: Du
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects; D010084:Oxidation-Reduction; D040901:Proteomics
chemical_list: D000970:Antineoplastic Agents; D003474:Curcumin