Novel effect of helenalin on Akt signaling and Skp2 expression in 3T3-L1 preadipocytes.
We have previously shown that the F-box protein, Skp2, is highly regulated during preadipocyte proliferation and plays a mechanistic role in p27 degradation during cell cycle progression. Data presented here demonstrate that the anti-inflammatory, anti-carcinogenic phytochemical, helenalin is a potent inhibitor of periodic Skp2 protein accumulation during early phases of 3T3-L1 adipocyte differentiation. Furthermore, helenalin was shown to completely block p27 degradation, cyclin A accumulation, and G(1)/S transition resulting in G(1) arrest. Helenalin was also shown to block Skp2 mRNA accumulation in a concentration-dependent manner and to completely suppress hormonally induced Skp2 promoter activity suggesting transcriptional mechanisms were involved. Examination of signaling events previously determined to be important for Skp2 upregulation during adipogenesis revealed impaired Akt phosphorylation immediately preceding the inhibitory effect of helenalin on Skp2 mRNA accumulation. These studies demonstrate a novel effect of helenalin on Skp2 regulation and growth factor receptor signaling during early stages of adipocyte differentiation.
Auld
Corinth A
CA
Department of Nutrition, The University of North Carolina at Greensboro, Greensboro, NC 27402, USA.
Hopkins
Robin G
RG
Fernandes
Karishma M
KM
Morrison
Ron F
RF
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D041721:3T3-L1 Cells / Q000187:drug effects; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011401:Promoter Regions, Genetic / Q000187:drug effects; D044786:S-Phase Kinase-Associated Proteins / Q000096:biosynthesis*; D012717:Sesquiterpenes / Q000494:pharmacology*; D045789:Sesquiterpenes, Guaiane; D015398:Signal Transduction / Q000187:drug effects*
D007328:Insulin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D044786:S-Phase Kinase-Associated Proteins; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; D050760:Cyclin-Dependent Kinase Inhibitor p27; C001329:helenalin; D003907:Dexamethasone; D015056:1-Methyl-3-isobutylxanthine