Apoptosis induction of 2'-hydroxycinnamaldehyde as a proteasome inhibitor is associated with ER stress and mitochondrial perturbation in cancer cells = 시남알데하이드 유도체의 세포사멸 유도 기전

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Title
Apoptosis induction of 2'-hydroxycinnamaldehyde as a proteasome inhibitor is associated with ER stress and mitochondrial perturbation in cancer cells = 시남알데하이드 유도체의 세포사멸 유도 기전
Author(s)
S H Hong; Jina Kim; J M Kim; So-Young Lee; Dae Seop Shin; Kwang Hee SonDong Cho Han; Y K Sung; Byoung-Mog Kwon
Bibliographic Citation
Biochemical Pharmacology, vol. 74, no. 4, pp. 557-565
Publication Year
2007
Abstract
2′-Hydroxycinnamaldehyde (HCA), isolated from the stem bark of Cinnamomum cassia, and 2′-benzoyloxycinnamaldehyde (BCA), one of HCA derivatives, have antiproliferative activities on several human cancer cell lines. Our previous study suggested that reactive oxygen species (ROS) and caspase-3 are the major regulators of HCA-induced apoptosis. In the present study, we demonstrated a novel molecular target using in vitro pull-down assay by biotin-labeled HCA (biotin-HCA) in SW620 cells. We analyzed 11 differential spots of 2-dimensional gel prepared with pull-downed proteins by biotin-HCA. Among them, five spots were identified as proteasome subunits. An in vitro 26S proteasome function assay using specific fluorogenic substrates showed that HCA potently inhibits L3-like activity of the proteasome. In addition, HCA showed inhibitory action against chymotrypsin-like, trypsin-like, and PGPH-like activities. DNA microarray showed that HCA induced heat shock family and ER stress-responsive genes, which reflects the accumulation of misfolded proteins by proteasome inhibition. On western blot analysis, it was confirmed that HCA induces glucose-regulated protein, 78 kDa (GRP78) and some representative endoplasmic reticulum (ER) stress-responsive proteins. Furthermore, HCA treatment decreased mitochondrial membrane potential. The effect of HCA on cytochrome c and Bax translocation between cytosol and mitochondrial membrane was clarified using western blot analysis. These results suggest that HCA-induced apoptosis is associated with the inhibition of the proteasome activity that leads in turn to the increase of ER stress and mitochondrial perturbation.
Keyword
2′-hydroxycinnamaldehydeapoptosisendoplasmic reticulummitochondriaproteasome
ISSN
0006-2952
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bcp.2007.05.016
Type
Article
Appears in Collections:
Division of Biomaterials Research > Industrial Bio-materials Research Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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