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1′‐Acetoxychavicol acetate induces an inhibition of tumor cell growth via a rapid and drastic modulation of glutathione metabolism
Author(s) -
MatsuiYuasa Isao,
KojimaYuasa Akiko,
Kennedy David Opare
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a565-e
Subject(s) - glutathione , intracellular , glutathione reductase , chemistry , glutathione peroxidase , glutathione synthetase , cell growth , biochemistry , gpx3 , growth inhibition , gpx6 , metabolism , enzyme
Background 1′‐Acetoxychavicol acetate (ACA), a compound naturally obtained from rhizomes and seeds of South East Asia plants, induces an inhibition of tumor cell growth through the reduction of intracellular sulhydryl groups. Here, we examined the activities of glutathione reductase (GR), a critical enzyme for the maintenance of the cellular GSH pool, and of other enzymes related in glutathione metabolism after ACA exposure. Results ACA caused a rapid and significant decrease in intracellular GSH and GSSG. When cells were incubated with 1 mM glutathione ethylester or 3 mM N‐acetyl cysteine, ACA‐induced decrease in cell viability was suppressed markedly. The cellular GR activity was reduced by more than 50% at 15 min after ACA exposure and the reduced activity was maintained until more than 120 min. Glutathione S‐transferase activity was also reduced by ACA exposure. However, the activity of glutathione peroxidase was not effect. Furthermore, we observed the accumulation of gamma‐glutamylcysteine, a substrate of glutathione synthetase, in ACA‐treated cells. Conclusion These results suggest that the rapid decrease in intracellular GSH levels through the reduction of GR activity and glutathione synthetase after addition of ACA triggers off an inhibition of tumor cell growth.