Curcumin induces changes in expression of genes involved in cholesterol homeostasis.
Curcuminoids, the yellow pigments of curcuma, exhibit anticarcinogenic, antioxidative and hypocholesterolemic activities. To understand the molecular basis for the hypocholesterolemic effects, we examined the effects of curcumin on hepatic gene expression, using the human hepatoma cell line HepG2 as a model system. Curcumin treatment caused an up to sevenfold, concentration-dependent increase in LDL-receptor mRNA, whereas mRNAs of the genes encoding the sterol biosynthetic enzymes HMG CoA reductase and farnesyl diphosphate synthase were only slightly increased at high curcumin concentrations where cell viability was reduced. Expression of the regulatory SREBP genes was moderately increased, whereas mRNAs of the PPARalpha target genes CD36/fatty acid translocase and fatty acid binding protein 1 were down-regulated. LXRalpha expression and accumulation of mRNA of the LXRalpha target gene ABCg1 were increased at low curcumin concentrations. Although curcumin strongly inhibited alkaline phosphatase activity, an activation of a retinoic acid response element reporter employing secreted alkaline phosphatase was observed. These changes in gene expression are consistent with the proposed hypocholesterolemic effect of curcumin.
Peschel
Dieter
D
BMBF Group Molecular Nutrition Halle, Institute of Nutritional Sciences, Martin-Luther University Halle-Wittenberg, D-06108 Halle, Germany.
Koerting
Ramona
R
Nass
Norbert
N
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D018955:CD36 Antigens / Q000235:genetics; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism*; D003474:Curcumin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D051228:Geranyltranstransferase / Q000235:genetics; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D008113:Liver Neoplasms; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics; D014162:Transfection
D000924:Anticholesteremic Agents; D018955:CD36 Antigens; D004268:DNA-Binding Proteins; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011973:Receptors, LDL; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D051228:Geranyltranstransferase; D003474:Curcumin