Document Detail

Mechanisms of cancer chemoprevention by hop bitter acids (beer aroma) through induction of apoptosis mediated by Fas and caspase cascades.
MedLine Citation:
PMID:  14709013     Owner:  NLM     Status:  MEDLINE    
The bitter acids of hops (Humulus lupulus L.) mainly consist of alpha-acids, beta-acids, and their oxidation products that contribute the unique aroma of the beer beverage. Hop bitter acids displayed a strong growth inhibitory effect against human leukemia HL-60 cells, with an estimated IC(50) value of 8.67 microg/mL, but were less effective against human histolytic lymphoma U937 cells. Induction of apoptosis was confirmed in HL-60 cells by DNA fragmentation and the appearance of a sub-G1 DNA peak, which were preceded by dissipation of mitochondrial membrane potential, cytochrome c release, and subsequent induction of pro-caspase-9 and -3 processing. Cleavages of PARP and DFF-45 were accompanied with activation of caspase-9 and -3 triggered by hop bitter acids in HL-60 cells. The change in the expression of Bcl-2, Bcl-X(L), and Bax in response to hop bitter acids was studied, and the Bcl-2 protein level slightly decreased; however, the Bcl-X(L) protein level was obviously decreased, whereas the Bax protein level was dramatically increased, indicating that the control of Bcl-2 family proteins by hop bitter acids might participate in the disruption of mitochondrial integrity. In addition, the results showed that hop bitter acids promoted the up-regulation of Fas and FasL prior to the processing and activation of pro-caspase-8 and cleavage of Bid, suggesting the involvement of a Fas-mediated pathway in hop bitter acids-induced cells. Taken together, these findings suggest that a certain intimate link might exist between receptor- and mitochondria-mediated death signalings that committed to cell death induced by hop bitter acids. The induction of apoptosis by hop bitter acids may offer a pivotal mechanism for their chemopreventive action.
Wei-Jen Chen; Jen-Kun Lin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of agricultural and food chemistry     Volume:  52     ISSN:  0021-8561     ISO Abbreviation:  J. Agric. Food Chem.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-07     Completed Date:  2004-02-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0374755     Medline TA:  J Agric Food Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  55-64     Citation Subset:  IM    
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
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MeSH Terms
Acids / analysis*
Anticarcinogenic Agents / pharmacology*
Antigens, CD95 / physiology*
Apoptosis / drug effects*
Caspases / metabolism*
Cell Survival / drug effects
Cytochromes c / metabolism
DNA Fragmentation / drug effects
Enzyme Activation
Fas Ligand Protein
HL-60 Cells
Humulus / chemistry*
Membrane Glycoproteins / physiology
Odors / analysis
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
bcl-2-Associated X Protein
bcl-X Protein
Reg. No./Substance:
0/Acids; 0/Anticarcinogenic Agents; 0/Antigens, CD95; 0/BAX protein, human; 0/BCL2L1 protein, human; 0/FASLG protein, human; 0/Fas Ligand Protein; 0/Membrane Glycoproteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 0/bcl-X Protein; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases

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