title: Differential proteomic analysis reveals that EGCG inhibits HDGF and activates apoptosis to increase the sensitivity of non-small cells lung cancer to chemotherapy.
abstract: OBJECTIVE
  To search for regulated proteins in response to green tea (-)-epigallocatechin-3-gallate (EGCG) in A549 lung cancer cells.
  
  
  METHODS
  2DE and ESI/multistage MS (ESI-MS/MS) were performed to identify modulated proteins in A549 cells treated with EGCG. Cell migration was evaluated by transwell assays. RNA interference was used to silence the hepatoma-derived growth factor (HDGF). Caspase-3, caspase-9, and HDGF were immunodetected by Western blot assays. Flow cytometry was used for detection of mitochondrial membrane potential and apoptosis.
  
  
  RESULTS
  We found that HDGF expression was threefold suppressed by EGCG treatment. Downregulation of HDGF by EGCG was confirmed using anti-HDGF antibodies in three lung cancer cell lines. EGCG treatment and HDGF abrogation by RNA interference resulted in a decreased migration of A549 cells. In addition, EGCG induced a marked synergistic effect with cisplatin in cell death. Consistently, an enhanced cytotoxicity in HDGF-silenced cells was also found. Cell death was associated to increased apoptosis, disruption of the mitochondrial membrane potential, and activation of caspase-3 and caspase-9.
  
  
  CONCLUSIONS
  Our data suggest for the first time that abrogation of HDGF by EGCG enhances cisplatin-induced apoptosis and sensitize A549 cells to chemotherapy. Therefore, we propose that decreasing the HDGF levels by using EGCG may represent a novel strategy in lung cancer therapy.
authors.affiliation: Genomics Sciences Program, Autonomous University of Mexico City, Mexico City, Mexico.
authors.forename: Ali
authors.initials: A
authors.lastname: Flores-Pérez
authors.affiliation: Molecular Biomedicine Program, National School of Medicine and Homeopathy, National Polytechnic Institute, Mexico.|Biotechnology Program, National School of Medicine and Homeopathy, National Polytechnic Institute, Mexico.
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Marchat
authors.affiliation: Genomics Sciences Program, Autonomous University of Mexico City, Mexico City, Mexico.
authors.forename: Lidia López
authors.initials: LL
authors.lastname: Sánchez
authors.affiliation: Genomics Sciences Program, Autonomous University of Mexico City, Mexico City, Mexico.
authors.forename: Diana
authors.initials: D
authors.lastname: Romero-Zamora
authors.affiliation: Natural Sciences Department, Metropolitan Autonomous University, Mexico.
authors.forename: Elena
authors.initials: E
authors.lastname: Arechaga-Ocampo
authors.affiliation: Genomics Sciences Program, Autonomous University of Mexico City, Mexico City, Mexico.
authors.forename: Nayeli
authors.initials: N
authors.lastname: Ramírez-Torres
authors.affiliation: Oncogenomics Laboratory, National Institute of Cancerology, Mexico.
authors.forename: José Díaz
authors.initials: JD
authors.lastname: Chávez
authors.affiliation: Lung Cancer Laboratory, National Institute of Respiratory Diseases, Mexico.
authors.forename: Ángeles
authors.initials: Á
authors.lastname: Carlos-Reyes
authors.affiliation: Laboratory of Translational Cancer Research and Cellular Therapy, Oncology Hospital, Medical Center Siglo XXI, Mexico.
authors.forename: Horacio
authors.initials: H
authors.lastname: Astudillo-de la Vega
authors.affiliation: Translational Medicine Laboratory, National Institute of Cancerology, Mexico.
authors.forename: Erika
authors.initials: E
authors.lastname: Ruiz-García
authors.affiliation: Genomics Sciences Program, Autonomous University of Mexico City, Mexico City, Mexico.
authors.forename: Abrahan
authors.initials: A
authors.lastname: González-Pérez
authors.affiliation: Genomics Sciences Program, Autonomous University of Mexico City, Mexico City, Mexico.
authors.forename: César
authors.initials: C
authors.lastname: López-Camarillo
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D040901:Proteomics; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor; D002392:Catechin; C045651:epigallocatechin gallate
keywords: Apoptosis; EGCG; HDGF; Lung cancer; Migration; Therapy