Effect of xanthohumol and isoxanthohumol on 3T3-L1 cell apoptosis and adipogenesis

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 i...

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Bibliographic Details
Published in:Apoptosis (London) 2007-11, Vol.12 (11), p.1953-1963
Main Authors: Yang, Jeong-Yeh, Della-Fera, Mary Anne, Rayalam, Srujana, Baile, Clifton A
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adenosine diphosphate
Adipogenesis - drug effects
Animals
Apoptosis
Apoptosis - drug effects
Cell Differentiation - drug effects
Cell Survival - drug effects
Cells
Fibroblasts - cytology
Fibroblasts - drug effects
Flavonoids
Growth Inhibitors - pharmacology
Humulus
Mice
Propiophenones - pharmacology
Proteins
Xanthones - pharmacology
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Summary: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 PPARgamma, C/EBPalpha, 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.
ISSN:1360-8185
1573-675X
DOI:10.1007/s10495-007-0130-4