title: Magnolol inhibits growth of gallbladder cancer cells through the p53 pathway.
abstract: Magnolol, the major active compound found in Magnolia officinalis has a wide range of clinical applications due to its anti-inflammation and anti-oxidation effects. This study investigated the effects of magnolol on the growth of human gallbladder carcinoma (GBC) cell lines. The results indicated that magnolol could significantly inhibit the growth of GBC cell lines in a dose- and time-dependent manner. Magnolol also blocked cell cycle progression at G0 /G1 phase and induced mitochondrial-related apoptosis by upregulating p53 and p21 protein levels and by downregulating cyclin D1, CDC25A, and Cdk2 protein levels. When cells were pretreated with a p53 inhibitor (pifithrin-a), followed by magnolol treatment, pifithrin-a blocked magnolol-induced apoptosis and G0 /G1 arrest. In vivo, magnolol suppressed tumor growth and activated the same mechanisms as were activated in vitro. In conclusion, our study is the first to report that magnolol has an inhibitory effect on the growth of GBC cells and that this compound may have potential as a novel therapeutic agent for the treatment of GBC.
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Maolan
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xu'an
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiangsong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Shanxi Medical University Second Hospital, Taiyuan, China.
authors.forename: Bingtai
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shanxi Medical University Second Hospital, Taiyuan, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Weng
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Shanxi Medical University Second Hospital, Taiyuan, China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Mu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Runfa
authors.initials: R
authors.lastname: Bao
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong, University School of Medicine, Shanghai, China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D005706:Gallbladder Neoplasms / Q000188:drug therapy / Q000473:pathology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008516:Medicine, Chinese Traditional; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D020687:cdc25 Phosphatases / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; C530104:CCND1 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017705:Lignans; D016159:Tumor Suppressor Protein p53; C005498:magnolol; D019938:Cyclin D1; D019001:Nitric Oxide Synthase; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases
keywords: Apoptosis; cell cycle arrest; gallbladder carcinoma; magnolol; p53 pathways