Up-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in left-sided human colon cancer.
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.
Notarnicola
Maria
M
Laboratory of Biochemistry, National Institute of Digestive Disease, Castellana Grotte, Bari, Italy.
Messa
Caterina
C
Pricci
Maria
M
Guerra
Vito
V
Altomare
Donato Francesco
DF
Montemurro
Severino
S
Caruso
Maria Gabriella
MG
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
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011973:Receptors, LDL; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases