Curcumin Induces Downregulation of E2F4 Expression and Apoptotic Cell Death in HCT116 Human Colon Cancer Cells; Involvement of Reactive Oxygen Species

Title
Curcumin Induces Downregulation of E2F4 Expression and Apoptotic Cell Death in HCT116 Human Colon Cancer Cells; Involvement of Reactive Oxygen Species
Author(s)
이추희김경찬[김경찬]
Keywords
I CLINICAL-TRIAL; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; PHASE; PROLIFERATION; FAMILY; IDENTIFICATION; INHIBITION; MECHANISMS; REPRESSION
Issue Date
201012
Publisher
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
Citation
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY, v.14, no.6, pp.391 - 397
Abstract
E2F transcription factors and their target genes have been known to play an important role in cell growth control. We found that curcumin, a polyphenolic phytochemical isolated from the plant Curcuma longa, markedly suppressed E2F4 expression in HCT116 colon cancer cells. Hydrogen peroxide was also found to decrease E2F4 protein level, indicating the involvement of reactive oxygen species (ROS) in curucmin-induced downregulation of E2F4 expression. Involvement of ROS in E2F4 downregulation in response to curcumin was confirmed by the result that pretreatment of cells with N-acetylcystein (NAC) before exposure of curcumin almost completely blocked the reduction of E2F4 expression at the protein as well as mRNA level. Anti-proliferative effect of curcumin was also suppressed by NAC which is consistent to previous reports showing curcumin-superoxide production and induction of poly (ADP-ribose) polymerase (PARP) cleavage as well as apoptosis. Expression of several genes, cyclin A, p21, and p27, which has been shown to be regulated in E2F4-dependent manner and involved in the cell cycle progression was also affected by curcumin. Moreover, decreased (cyclin A) and increased (p21 and p27) expression of these E2F4 downstream genes by curcumin was restored by pretreatment of cells with NAC and E2F4 overexpression which is induced by doxycycline. In addition, E2F4 overexpression was observed to partially ameliorate curcumin-induced growth inhibition by cell viability assay. Taken together, we found curcumin-induced ROS down-regulation of E2F4 expression and modulation of E2F4 target genes which finally lead to the apoptotic cell death in HCT116 colon cancer cells, suggesting that E2F4 appears to be a novel determinant of curcumin-induced cytotoxicity.
URI
http://hdl.handle.net/YU.REPOSITORY/23228http://dx.doi.org/10.4196/kjpp.2010.14.6.391
ISSN
1226-4512
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의과대학 > 생화학.분자생물학교실 > Articles
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