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Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5).

Authors
Jung, EM; Lim, JH; Lee, TJ; Park, JW; Choi, KS; Kwon, TK
Citation
Carcinogenesis, 26(11):1905-1913, 2005
Journal Title
Carcinogenesis
ISSN
0143-33341460-2180
Abstract
Curcumin exhibits anti-inflammatory and antitumor activities. Although its functional mechanism has not been elucidated so far, numerous studies have shown that curcumin induces apoptosis in cancer cells. In the present study, we show that subtoxic concentrations of curcumin sensitize human renal cancer cells to the tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. This apoptosis induced by the combination of curcumin and TRAIL is not interrupted by Bcl-2 overexpression. We found that treatment with curcumin significantly induces death receptor 5 (DR5) expression both at its mRNA and protein levels, accompanying the generation of the reactive oxygen species (ROS). Not only the pretreatment with N-acetylcystine but also the ectopic expression of peroxiredoxin II, an antioxidative protein, dramatically inhibited the apoptosis induced by curcumin and TRAIL in combination, blocking the curcumin-mediated DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by ROS-mediated DR5 upregulation.
MeSH terms
Antineoplastic Agents/pharmacology*Antioxidants/pharmacologyApoptosis/drug effects*Apoptosis Regulatory Proteins/pharmacology*Carcinoma, Hepatocellular/drug therapyCarcinoma, Hepatocellular/metabolismCarcinoma, Hepatocellular/pathologyCaspases/antagonists & inhibitorsCaspases/metabolismColonic Neoplasms/drug therapyColonic Neoplasms/metabolismColonic Neoplasms/pathologyCurcumin/pharmacology*Cystine/analogs & derivativesCystine/pharmacologyCytochromes c/metabolismDrug CombinationsDrug Resistance, Neoplasm/drug effects*Enzyme Activation/drug effectsFlow CytometryHumansLiver Neoplasms/drug therapyLiver Neoplasms/metabolismLiver Neoplasms/pathologyLuciferasesMembrane Glycoproteins/pharmacology*Peroxidases/pharmacologyPeroxiredoxinsPromoter Regions, GeneticProto-Oncogene Proteins c-bcl-2/metabolismReactive Oxygen Species*Receptors, TNF-Related Apoptosis-Inducing LigandReceptors, Tumor Necrosis Factor/geneticsReceptors, Tumor Necrosis Factor/metabolism*TNF-Related Apoptosis-Inducing LigandTumor Cells, CulturedTumor Necrosis Factor-alpha/pharmacology*Up-Regulation
DOI
10.1093/carcin/bgi167
PMID
15987718
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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