Synergic effect of eicosapentaenoic acid and lovastatin on gene expression of HMGCoA reductase and LDL receptor in cultured HepG2 cells.
BACKGROUND
PUFAs are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme catalyzing the conversion of HMGCoA to mevalonate, the rate limiting step in cholesterol biosynthesis. Statins represent a class of drugs that are widely used to treat hypercholesterolemia for their ability to inhibit cholesterol biosynthesis and to up-regulate the synthesis of Low Density Lipoprotein (LDL) receptors in the liver. PUFAs mediate many, if not all, actions of statins and this could be one mechanism by which they lower cholesterol levels. The purpose of this study was to investigate whether combined treatment with Eicosapentaenoic acid (EPA) and lovastatin enhanced the regulatory effect on gene expression of HMGCoA reductase and LDL receptor in HepG2 cell line.


RESULTS
The combined treatment with EPA and lovastatin enhanced the regulatory effect on gene expression of HMGCoA reductase and LDL receptor in HepG2 cell line. Moreover, we detected a synergistic effect on the inhibition of cancer cell proliferation obtained by combination of EPA and Lovastatin.


CONCLUSIONS
The use of EPA, in combination with low doses of Lovastatin may have potential value in treatment of neoplastic diseases.
Laboratory of Biochemistry, National Institute for Digestive Diseases Castellana Grotte, Bari, Italy. maria.notarnicola@irccsdebellis.it
Maria
M
Notarnicola
Caterina
C
Messa
Maria G
MG
Refolo
Valeria
V
Tutino
Angelica
A
Miccolis
Maria G
MG
Caruso
D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology*; D011973:Receptors, LDL / Q000378:metabolism*
D011973:Receptors, LDL; D008148:Lovastatin; D015118:Eicosapentaenoic Acid; D006903:Hydroxymethylglutaryl CoA Reductases