title: Antiproliferative effects of novel aliphatic acetogenin analogs against aggressive solid tumor cell lines.
abstract: The antiproliferative effects of three synthetic analogs of aliphatic acetogenins selected from a previous screening were compared to those of the drugs used for the treatment of malignant pleural mesothelioma (MPM) and pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  Four PDAC and three MPM cell lines were used in the study. Cell growth inhibition was determined after 48 h exposure to the drugs. Cell-cycle disruption and apoptosis induction were studied by flow cytometry. The modulation of Akt phosphorylation was studied using a specific ELISA for P-Ser473 Akt.
  
  
  RESULTS
  The new compounds inhibited cell growth, induced apoptosis and cell-cycle abrogation in all cell lines. Phosphorylated Akt levels rose after treatment.
  
  
  CONCLUSIONS
  The results demonstrated better performance of aliphatic acetogenin analogs against PDAC cells when compared to standard anticancer drugs. For MPM cells, the application of the new compounds may play an important role in overcoming the resistance to conventional treatments.
authors.affiliation: BioLab, Instituto Universitario de Bio-Orgánica Antonio González (IUBO-AG), Universidad de La Laguna, C/ Astrofísico Francisco Sánchez 2, 38206 La Laguna, Spain. lgleon@ull.es
authors.forename: Leticia G
authors.initials: LG
authors.lastname: León
authors.forename: Elisa
authors.initials: E
authors.lastname: Giovannetti
authors.forename: Claudia
authors.initials: C
authors.lastname: Alecci
authors.forename: Fiorella
authors.initials: F
authors.lastname: Giancola
authors.forename: Niccola
authors.initials: N
authors.lastname: Funel
authors.forename: Paolo
authors.initials: P
authors.lastname: Zucali
authors.forename: Godefridus J
authors.initials: GJ
authors.lastname: Peters
authors.forename: José M
authors.initials: JM
authors.lastname: Padrón
mesh_terms: D054378:Acetogenins / Q000737:chemistry / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008654:Mesothelioma / Q000378:metabolism / Q000473:pathology; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010997:Pleural Neoplasms / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D054378:Acetogenins; D051057:Proto-Oncogene Proteins c-akt