Effect of xanthohumol and isoxanthohumol on 3T3-L1 cell apoptosis and adipogenesis
Title
Effect of xanthohumol and isoxanthohumol on 3T3-L1 cell apoptosis and adipogenesis
Publication type
Journal Article
Year of Publication
2007
Authors
Journal
Apoptosis
Volume
12
Issue
11
Pagination
1953 - 1963
Date published
2007
ISBN
13608185 (ISSN)
Keywords
3T3-L1 Cells, adipocyte, adipogenesis, animal cell, Animals, antioxidant, apoptosis, article, ascorbic acid, caspase 3, caspase 7, Caspase-3/7, CCAAT/enhancer binding protein α (C/EBPα), cell differentiation, cell maturation, cell strain 3T3, Cell Survival, cell viability, cytochrome c, drug effect, embryo, enzyme activation, fibroblast, Fibroblasts, Growth Inhibitors, Humulus, immunoblotting, isoxanthohumol, lipid, mercaptoethanol, Mice, Mitochondrial membrane potential, mouse, nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1, nonhuman, peroxisome proliferator activated receptor gamma, Peroxisome proliferator-activated receptor γ (PPARγ), priority journal, Propiophenones, reactive oxygen metabolite, Reactive Oxygen Species, unclassified drug, xanthohumol, Xanthones
Abstract
Xanthohumol (XN), the chalcone from beer hops has several biological activities. XN has been shown to induce apoptosis in cancer cells and also has been reported to be involved in lipid metabolism. Based on these studies and our previous work with natural compounds, we hypothesized that XN and its isomeric flavanone, isoxanthohumol (IXN), would induce apoptosis in adipocytes through the mitochondrial pathway and would inhibit maturation of preadipocytes. Adipocytes were treated with various concentrations of XN or IXN. In mature adipocytes both XN and IXN decreased viability, increased apoptosis and increased ROS production, XN being more effective. Furthermore, the antioxidants ascorbic acid and 2-mercaptoethanol prevented XN and IXN-induced ROS generation and apoptosis. Immunoblotting analysis showed an increase in the levels of cytoplasmic cytochrome c and cleaved poly (ADP-ribose) polymerase (PARP) by XN and IXN. Concomitantly, we observed activation of the effectors caspase-3/7. In maturing preadipocytes both XN and IXN were effective in reducing lipid content, XN being more potent. Moreover, the major adipocyte marker proteins such as PPARγ, C/EBPα, and aP2 decreased after treatment with XN during the maturation period and that of DGAT1 decreased after treatment with XN and IXN. Taken together, our data indicate that both XN and IXN inhibit differentiation of preadipocytes, and induce apoptosis in mature adipocytes, but XN is more potent.