Abstract
Background/Aims: Human hepatoma cells have been reported to be resistant to Fas-mediated apoptosis.
Sodium butyrate (SB) induced apoptosis of several cancer cells. We investigated the
effects of SB on Fas-mediated apoptosis of hepatoma cells.
Methods: In hepatoma cells (HuH-6, HuH-7, Hep-G2, and PLC/PRF/5), susceptibility to Fas-mediated
apoptosis and Fas expression were assessed. Caspase-3 activation and cell cycle progression
were evaluated in HuH-6. A cDNA microarray assay was performed to screen the changes
in the expression of mRNAs.
Results: Pretreatment with SB caused an enhancement of the sensitivity to anti-Fas-mediated
cytotoxicity, though it did not increase the expression of Fas. The cDNA microarray
assay revealed up-regulation of pro-apoptotic Bik, Bak, Bid and c-Jun N-terminal protein
kinase-1, and down-regulation of anti-apoptotic Bag-1 and cellular Fas-associated
death domain-like interleukin-1β-converting enzyme inhibitor protein. In some molecules,
expression of the proteins was confirmed by Western blotting. An increase in truncated-Bid
accompanying the reduction in Bid was also observed.
Conclusions: SB enhances the susceptibility of hepatoma cells to anti-Fas-mediated cytotoxicity
by altering the mRNA and protein expression and/or the activation status of proteins
that could be involved in the Fas signaling pathway. SB may have an important role
in the elimination of hepatoma cells.
Keywords
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Article info
Publication history
Accepted:
September 22,
2003
Received in revised form:
September 10,
2003
Received:
April 9,
2003
Identification
Copyright
© 2003 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
