title: Anti-tumor effect of germacrone on human hepatoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis.
abstract: Germacrone is one of the main bioactive components in the traditional Chinese medicine Rhizoma curcuma. In this study, the anti-proliferative effect of germacrone on the human hepatoma cell lines and the molecular mechanism underlying the cytotoxicity of germacrone were investigated. Treatment of human hepatoma cell lines HepG2 and Bel7402 with germacrone resulted in cell cycle arrest and apoptosis in a dose-dependent manner as measured by MTT assay, flow cytometric and fluorescent microscopy analysis, while much lower effect on normal human liver cell L02 was observed. Flow cytometric analysis revealed that germacrone induced G2/M arrest in the cell cycle progression that was associated with an obvious decrease in the protein expression of cyclin B1 and its activating partner CDK1 with concomitant inductions of p21. Hoechst 33258 and Annexin V/PI staining results showed that the total cell number in apoptosis associated with a dose-dependent up-regulation of Bax and down-regulation of Bcl-2/Bcl-xl was increased. In the meantime, the up-regulation of p53 and reactive oxygen species increase were observed, which suggested that germacrone might be a new potent chemopreventive drug candidate for liver cancer via regulating the expression of proteins related to G2/M cell cycle and apoptosis, and p53 and oxidative damage may play important roles in the inhibition of human hepatoma cells growth by germacrone.
authors.affiliation: The Genetic Engineering International Cooperation Base of Ministry of Science and Technology, Chinese National Center of Plant Gene HUST Part, College of Life Science and Technology, Huazhong University of Science & Technology, Luoyu Road 1037, Wuhan 430074, Hubei, China.
authors.forename: Yunyi
authors.initials: Y
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Fang
authors.forename: Fengyun
authors.initials: F
authors.lastname: Ma
authors.forename: Qian
authors.initials: Q
authors.lastname: Zheng
authors.forename: Pengyi
authors.initials: P
authors.lastname: Deng
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhao
authors.forename: Mingjie
authors.initials: M
authors.lastname: Chen
authors.forename: Guangxiao
authors.initials: G
authors.lastname: Yang
authors.forename: Guangyuan
authors.initials: G
authors.lastname: He
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056744:Cyclin B1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology*; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D045788:Sesquiterpenes, Germacrane / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D045788:Sesquiterpenes, Germacrane; D016159:Tumor Suppressor Protein p53; C048393:germacrone; D016203:CDC2 Protein Kinase