title: A synthetic curcumin derivative hydrazinobenzoylcurcumin induces autophagy in A549 lung cancer cells.
abstract: BACKGROUND
  Curcumin exhibits growth-suppressive activity against a variety of cancer cells, but low bioavailability restricts its application in chemotherapeutic trials. Nowadays, a growing number of curcumin derivatives or analogs are known, hoping to replace curcumin and circumvent this problem. Hydrazinobenzoylcurcumin (HBC) has been synthesized and identified as a potent inhibitor of cell proliferation in previous reports.
  
  
  OBJECTIVE
  This study presents a novel mechanism of cell autophagy induced by HBC in the human non-small lung epithelial carcinoma (A549) cells.
  
  
  METHODS
  Cells were cultured and treated with HBC at different concentrations (10-80 μM) and at different time periods (1-24 h). Microscopic analysis was used to detect the morphology changes and autophagolysosomes of A549 cells. An acridine orange staining assay was conducted to evaluate the autophagolysosomes and autophagic vacuoles was analyzed by monodansylcadaverine (MDC) and GFP-LC3 transfection analysis. Western blotting was used to assess the conversion of microtubule-associated protein light chain 3 (LC3).
  
  
  RESULTS
  HBC could induce A549 cells autophagolysosomes formation in a dose and time-dependent manner and the inhibitory rate of HBC (80 μM) on the viability of A549 cells reached 76.68 ± 5.81% after 24 h of treatment. Autophagic vacuoles increased in a concentration-dependent manner in HBC-treated cell. Furthermore, conversion of LC3-I to LC3-II, accumulation of GFP-tagged LC3 positive intracellular vacuoles and increased fusion of autophagosomes with lysosomes suggested the occurrence of autophagy.
  
  
  CONCLUSIONS
  Our data indicate that HBC induced A549 cell autophagy, which is a novel cell death mechanism induced by curcumin derivatives.
authors.affiliation: College of Bioengineering .
authors.forename: Guang-Zhou
authors.initials: GZ
authors.lastname: Zhou
authors.forename: Shuai-Na
authors.initials: SN
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Gang-Chun
authors.initials: GC
authors.lastname: Sun
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D011720:Pyrazoles; C000591373:hydrazinobenzoylcurcumin; D049452:Green Fluorescent Proteins; D003474:Curcumin