title: Anti-tumor effect of evodiamine by inducing Akt-mediated apoptosis in hepatocellular carcinoma.
abstract: Evodiamine is an alkaloid extracted from Euodia rutaecarpa (Juss.) Benth. There is little information about the mechanisms of evodiamine on the apoptosis of hepatocellular carcinoma (HCC).
  
  
  
  A xenograft model and CCK8 assay were used to investigate the anti-HCC effect of evodiamine. The effect of evodiamine on apoptosis was evaluated by DAPI staining and flow cytometry. Western blot analyses and immunohistochemistry were processed to assess the protein expressions of Akt and apoptotic proteins.
  
  
  
  Evodiamine suppressed tumor growth, improved the expression of cleaved-caspase3 and decreased tumor specific growth factor (TSGF) and alpha fetoprotein (AFP) activities. Furthermore, evodiamine inhibited cell viability and induced cell cycle arrest. DAPI staining revealed nuclear condensation in evodiamine-treated groups. Meanwhile, evodiamine increased the number of apoptotic cells. Furthermore, evodiamine suppressed Akt and regulated apoptotic proteins in HepG2 cells. Evodiamine decreased p-Akt levels activated by SC79, which led to the increase of bax/bcl-2 and cleaved-caspase3.
  
  
  
  Our findings suggested that evodiamine could exert anti-HCC effect through inducing Akt-mediated apoptosis. Evodiamine has the potential to be a therapeutic medicine for HCCs.
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China. Electronic address: shilehappy@163.com.
authors.forename: Le
authors.initials: L
authors.lastname: Shi
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liang
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Ji
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
authors.forename: Guangji
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Animal Core Facility of Nanjing Medical University, Nanjing Medical University, Nanjing 210000, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang 222002, PR China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China. Electronic address: xuliglp@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D032086:Evodia / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011799:Quinazolines; C049639:evodiamine; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3
keywords: Akt; Apoptosis; Evodiamine; Hepatocellular carcinoma