Enhanced effects of xanthohumol plus honokiol on apoptosis in 3T3-L1 adipocytes.
OBJECTIVE
To study the effects of xanthohumol (XN), a flavonoid found in hops (Humulus lupulus) and honokiol (HK), a lignan isolated from Magnolia officinalis, alone and in combination, on apoptotic signaling in 3T3-L1 adipocytes.


METHODS
3T3-L1 mature adipocytes were incubated with various concentrations of XN and HK alone and in combination. Viability and apoptosis were quantified using an MTS-based cell viability assay and single-stranded DNA assay, respectively. Expression of apoptosis related proteins including cleaved poly(ADP-ribose) polymerase (PARP), cytochrome c, Bcl-2, caspase-3/7, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Akt was analyzed by western blotting.


RESULTS
Combinations of XN and HK significantly decreased viability and induced apoptosis in a dose-dependent manner and more than the additive responses to XN and HK alone. Western blot analysis showed an increase in cleaved PARP and cytochrome c release and decrease in expression of Bcl-2 protein by XN plus HK, whereas XN and HK individually had no effect. Furthermore, the combination of XN and HK activated PTEN and inactivated Akt by decreasing levels of phosphorylated PTEN and phosphorylated Akt.


CONCLUSIONS
We demonstrated that although XN and HK showed little or no effect as individual compounds, in combination (XN plus HK) they showed enhanced activity in inducing apoptosis via the cytochrome c/caspase-3/PARP and PTEN/Akt pathways in 3T3-L1 adipocytes.
Yang
Jeong-Yeh
JY
Department of Animal and Dairy Science, University of Georgia, Athens, Georgia, USA.
Della-Fera
Mary Anne
MA
Rayalam
Srujana
S
Baile
Clifton A
CA
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005419:Flavonoids; D017705:Lignans / Q000494:pharmacology*; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011427:Propiophenones / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000498:Allyl Compounds; D010636:Phenols
D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D053148:Caspase 3; D045304:Cytochromes c; D005419:Flavonoids; D017705:Lignans; D051059:PTEN Phosphohydrolase; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011427:Propiophenones; D051057:Proto-Oncogene Proteins c-akt; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C499321:Parp1 protein, mouse; C487757:Pten protein, mouse; C104536:xanthohumol