title: Treatment of undifferentiated colorectal cancer cells with fish-oil derived docosahexaenoic acid triggers caspase-3 activation and apoptosis.
abstract: BACKGROUND
  The effectiveness of chemotherapy is often limited by the side effects on normal tissues. Consequently, the search for new therapeutic agents with minimal toxicity is of particular interest in cancer management. Many studies have shown that docosahexaenoic acid (DHA) have cytotoxic effects against different kinds of cancer cells. However, little attention has been paid to explore the effect of DHA on undifferentiated colorectal cancer cells. In this study, the effects of DHA on LS174T cells as an early stage of tumor initiation were investigated.
  
  
  METHODS
  Tumor cells were treated to various concentrations of DHA and proliferation, survivin expression, caspase-3 activation, and apoptosis were evaluated by different cellular and molecular techniques.
  
  
  RESULTS
  Following 48 h treatment, proliferation was measured to be 73 ± 4.5% (P = 0.000), 53 ± 5.7% (P = 0.000) and 26.3 ± 3.5% (P = 0.000) for 50, 100, and 150 µM DHA, respectively compared to untreated cells. This molecule induced 63% (P = 0.001) and 46% (P = 0.000) decrease in survivin messenger ribonucleic acid (mRNA) level as well as 1.8 (P = 0.001) and three-fold (P = 0.000) increase in caspase-3 activation for 50 and 100 µM DHA, respectively compared to untreated cells. Our evidence showed that survivin mRNA is expressed at the early stage of colorectal cancer cells and DHA-treated cells expressed markedly a lower survivin mRNA compared to untreated cells.
  
  
  CONCLUSIONS
  DHA is an attractive repressor of survivin expression, increases caspase-3 and apoptosis in colorectal cancer cells and may provide a novel approach to the treatment of colorectal cancer at the early stage of tumor initiation.
authors.affiliation: Department of Histology and Embryology, Faculty of Science; Department of Cellular and Molecular Biotechnology, Institute of Biotechnology, Urmia, Iran.
authors.forename: Parinaz
authors.initials: P
authors.lastname: Ahangar
authors.affiliation: Department of Histology and Embryology, Faculty of Science; Department of Cellular and Molecular Biotechnology, Institute of Biotechnology; Royan Stem Cell Technology Company, West Azarbaijan Cord Blood Bank, Urmia, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Sam
authors.affiliation: Department of Histology and Embryology, Faculty of Science, Institute of Biotechnology, Urmia, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Nejati
authors.affiliation: Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Habibian
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005395:Fish Oils / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D060787:Neoplasm Grading; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D005395:Fish Oils; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D004281:Docosahexaenoic Acids; D053148:Caspase 3