J Agric Food Chem. 2004 Jan 14;52(1):55-64. Links
Mechanisms of Cancer Chemoprevention by Hop Bitter Acids (Beer Aroma) through Induction of Apoptosis
Mediated by Fas and Caspase Cascades.
Chen WJ, Lin JK.
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University,
Taipei, Taiwan.
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.
PMID: 14709013 [PubMed - in process]
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