|
KMID : 0613820080180030336
|
|
Journal of Life Science
2008 Volume.18 No. 3 p.336 ~ p.343
|
|
|
Induction of Apoptosis by HDAC Inhibitor Trichostatin A through Activation of Caspases and in Human Prostate Epithelial Cells
|
|
Park Cheol
Kim Cheng-Yun
Choi Byung-Tae
Lee Won-Ho
Choi Yung-Hyun
|
|
|
Abstract
|
|
|
|
Histone deacetylases (HDACs) inhibitors have emerged as the accessory therapeutic agents for various human cancers, since they can block the activity of specific HDACs, restore the expression of some tumor suppressor genes and induce cell differentiation, cell cycle arrest and apoptosis in vitro and in vivo. In the present study, we investigated that the effect of trichostatin A (TSA), an HDAC inhibitor, on the cell growth and apoptosis, and its effect on the nuclear factor-kappaB (NF-xB) activity in 267B1 human prostate epithelial cells. Exposure of 267B1 cells to TSA resulted in growth inhibition and apoptosis induction in and dose-dependent manners as measured by fluorescence microscopy, agarose gel electrophoresis and flow cytometry analysis. TSA treatment inhibited the levels of IAP family members such as c-IAP-1 and c-IAP-2 and induced the proteolytic activation of caspase-3, -8 and -9, which were associated with concomitant degradation of poly (ADP-ribose)-polymerase, and laminin B proteins. The increase in apoptosis by TSA was connected with the translocation of NF-xB from cytosol to nucleus, increase of the DNA binding as well as promoter activity of NF-xB , and degradation of cytosolic inhibitor of KappaB protein. We therefore concluded that TSA demonstrated anti-proliferative and apoptosis-inducing effects on 267B1 cells in vitro, and that the activation of caspases and NF-xB may play important roles in its mechanism of action. Although further studies are needed, these findings provided important insights into the possible molecular mechanisms of the anti-cancer activity of TSA.
|
|
|
KEYWORD
|
|
|
Histone deacetylases inhibitor, 267B1, apoptosis, caspase, nuclear factor-kappaB
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|