title: Glabridin induces apoptosis and autophagy through JNK1/2 pathway in human hepatoma cells.
abstract: BACKGROUND
  Extensive research results support the use of herbal medicine or natural food to augment therapy for various cancers. Studies have associated glabridin with numerous biological activities, such as regulating energy metabolism and estrogenic, neuroprotective, antiosteoporotic, and skin-whitening activities.
  
  
  OBJECTIVE
  However, how glabridin affects tumor cell autophagy has not been clearly determined.
  
  
  METHODS
  Autophagy is a lysosomal degradation pathway essential for cell survival and tissue homeostasis. In this study, the roles of autophagy and related signaling pathways during glabridin-induced autophagy in human liver cancer cells were investigated. Additionally, the molecular mechanism of the anticancer effects of glabridin in human hepatoma cells was investigated.
  
  
  RESULTS
  The results revealed that glabridin significantly inhibited cell proliferation in human hepatoma cells. Glabridin induced apoptosis dose-dependently in Huh7 cells through caspase-3, -8, and -9 activation and PARP cleavage. Furthermore, autophagy was detected as early as 12h after exposure to a low dose of glabridin, as indicated by the up-regulated expression of LC3-II and beclin-1 proteins. The inhibition of JNK1/2 and p38 MAPK by specific inhibitors significantly reduced glabridin-induced activation of caspases-3, -8, and -9. Blocking autophagy sensitize the Huh7 cells to apoptosis.
  
  
  CONCLUSIONS
  This study demonstrated for the first time that autophagy occurs earlier than apoptosis does during glabridin-induced apoptosis in human liver cancer cell lines. Glabridin induces Huh7 cell death through apoptosis through the p38 MAPK and JNK1/2 pathways and is a potential chemopreventive agent against human hepatoma.
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua 50006, Taiwan; School of Optometry, Chung Shan Medical University, Taichung 40201, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan.
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.affiliation: Department of Surgical Pathology, Changhua Christian Hospital, Changhua 500, Taiwan; Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan; School of Medicine, Chung Shan Medical University, Taichuang 40201, Taiwan.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Hsieh
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua 50006, Taiwan.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Lo
authors.affiliation: Cancer Research Center, Changhua Christian Hospital, Changhua 50006, Taiwan.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Chuang
authors.affiliation: School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. Electronic address: hlchiou@csmu.edu.tw.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Chiou
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan. Electronic address: ysf@csmu.edu.tw.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006035:Glycyrrhiza / Q000737:chemistry*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D007529:Isoflavones; D008565:Membrane Proteins; D010636:Phenols; D010936:Plant Extracts; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; C107601:glabridin
keywords: Apoptosis; Autophagy; Glabridin; Hepatoma; JNK