title: Up-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in left-sided human colon cancer.
abstract: BACKGROUND
  We evaluated the HMGCoA reductase activity and LDL receptor levels in human colon cancer as well as the effects of simvastatin on in vitro cell growth and apoptosis of DLD-1 and Caco2 cell lines.
  
  
  METHODS
  HMGCoA reductase activity and LDL receptor were measured by radiochemical assay and ELISA method, respectively. Cell growth and apoptosis were evaluated by MTT-test and DNA fragmentation analysis, respectively.
  
  
  RESULTS
  Higher HMGCoA reductase activity and LDL receptor levels were detected in cancer than in normal mucosa. An up-regulation of HMGCoA reductase activity was detected in left-sided tumors. Simvastatin treatment produced marked anti-proliferative and pro-aptotic effects in DLD-1. Cell growth inhibition, but no apoptosis, was also evident in Caco2 cells.
  
  
  CONCLUSIONS
  The cholesterol pathway is involved in colon malignant transformation. Therapeutic strategies using HMGCoA reductase inhibitors as anti-cancer compounds should also take into consideration the biological and clinical differences detected inside colon tracts.
authors.affiliation: Laboratory of Biochemistry, National Institute of Digestive Disease, Castellana Grotte, Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Notarnicola
authors.forename: Caterina
authors.initials: C
authors.lastname: Messa
authors.forename: Maria
authors.initials: M
authors.lastname: Pricci
authors.forename: Vito
authors.initials: V
authors.lastname: Guerra
authors.forename: Donato Francesco
authors.initials: DF
authors.lastname: Altomare
authors.forename: Severino
authors.initials: S
authors.lastname: Montemurro
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Caruso
mesh_terms: D000368:Aged; D018938:Caco-2 Cells; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008297:Male; D011973:Receptors, LDL / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011973:Receptors, LDL; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases