title: Mechanism of cytotoxic action of crambescidin-816 on human liver-derived tumour cells.
abstract: OBJECTIVE
  Marine sponges have evolved the capacity to produce a series of very efficient chemicals to combat viruses, bacteria, and eukaryotic organisms. It has been demonstrated that several of these compounds have anti-neoplastic activity. The highly toxic sponge Crambe crambe has been the source of several molecules named crambescidins. Of these, crambescidin-816 has been shown to be cytotoxic for colon carcinoma cells. To further investigate the potential anti-carcinogenic effect of crambescidin-816, we analysed its effect on the transcription of HepG2 cells by microarray analysis followed by experiments guided by the results obtained.
  
  
  METHODS
  After cytotoxicity determination, a transcriptomic analysis was performed to test the effect of crambescidin-816 on the liver-derived tumour cell HepG2. Based on the results obtained, we analysed the effect of crambescidin-816 on cell-cell adhesion, cell-matrix adhesion, and cell migration by Western blot, confocal microscopy, flow cytometry and transmission electron microscopy. Cytotoxicity and cell migration were also studied in a variety of other cell lines derived from human tumours.
  
  
  RESULTS
  Crambescidin-816 had a cytotoxic effect on all the cell lines studied. It inhibited cell-cell adhesion, interfered with the formation of tight junctions, and cell-matrix adhesion, negatively affecting focal adhesions. It also altered the cytoskeleton dynamics. As a consequence of all these effects on cells crambescidin-816 inhibited cell migration.
  
  
  CONCLUSIONS
  The results indicate that crambescidin-816 is active against tumour cells and implicate a new mechanism for the anti-tumour effect of this compound.
authors: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela (USC), Lugo, Spain.
authors: J A
authors: JA
authors: Rubiolo
authors: H
authors: H
authors: López-Alonso
authors: M
authors: M
authors: Roel
authors: M R
authors: MR
authors: Vieytes
authors: O
authors: O
authors: Thomas
authors: E
authors: E
authors: Ternon
authors: F V
authors: FV
authors: Vega
authors: L M
authors: LM
authors: Botana
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002450:Cell Communication / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness; D013141:Spiro Compounds / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D013141:Spiro Compounds; C083155:crambescidin 816
keywords: crambescidin-816; transcriptomic analysis; tumour cell adhesion; tumour cell migration; tumour cell viability