title: B19, a novel monocarbonyl analogue of curcumin, induces human ovarian cancer cell apoptosis via activation of endoplasmic reticulum stress and the autophagy signaling pathway.
abstract: BACKGROUND
  The unfolded protein response, autophagy and endoplasmic reticulum (ER) stress-induced apoptosis regulate tumor cell fate and have become novel signaling targets for the development of cancer therapeutic drugs. Curcumin has been used to treat several different cancers, including ovarian cancer, in clinical trials and research; however, the role of ER stress and autophagy in the therapeutic effects of curcumin and new curcumin analogues remains unclear.
  
  
  METHODS
  Cell viability was determined using the MTT assay. Apoptosis was detected using flow cytometry with PI/Annexin V-FITC staining. The expression levels of ER stress- and autophagy-related proteins were analyzed by western blotting. The activation of autophagy was detected using immunofluorescence staining.
  
  
  RESULTS
  We demonstrated that B19 induced HO8910 cell apoptosis in a dose-responsive manner. We also determined and that this effect was associated with corresponding increases in a series of key components in the UPR and ER stress-mediated apoptosis pathways, followed by caspase 3 cleavage and activation. We also observed that B19 treatment induced autophagy in HO8910 cells. The inhibition of autophagy using 3-methyladenine (3-MA) increased levels of intracellular misfolded proteins, which enhanced ovarian cancer apoptosis.
  
  
  CONCLUSIONS
  Our data indicate that ER stress and autophagy may play a role in the apoptosis that is induced by the curcumin analogue B19 in an epithelial ovarian cancer cell line and that autophagy inhibition can increase curcumin analogue-induced apoptosis by inducing severe ER stress.
authors: Department of Gynecology and Obstetrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
authors: Wanglei
authors: W
authors: Qu
authors: Jian
authors: J
authors: Xiao
authors: Hongyu
authors: H
authors: Zhang
authors: Qiong
authors: Q
authors: Chen
authors: Zhouguang
authors: Z
authors: Wang
authors: Hongxue
authors: H
authors: Shi
authors: Liang
authors: L
authors: Gong
authors: Jianqiang
authors: J
authors: Chen
authors: Yanlong
authors: Y
authors: Liu
authors: Risheng
authors: R
authors: Cao
authors: Jieqiang
authors: J
authors: Lv
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008854:Microscopy, Electron; D015398:Signal Transduction / Q000502:physiology*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: C587237:B19 monocarbonyl curcumin; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D003474:Curcumin
keywords: B19; Curcumin analogues; ER stress; apoptosis; autophagy.; ovarian cancer
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