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Curcumin attenuates cytochrome P450 induction in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin by ROS-dependently degrading AhR and ARNT

Cited 39 time in Web of Science Cited 41 time in Scopus
Authors
Choi, Hyunsung; Chun, Yang-Sook; Shin, Yong Jae; Ye, Sang Kyu; Kim, Myung-Suk; Park, Jong-Wan
Issue Date
2008-11-21
Publisher
Wiley-Blackwell
Citation
Cancer Sci. 2008; 99(12): 2518-2524
Keywords
Antigens, Polyomavirus Transforming/physiologyAryl Hydrocarbon Receptor Nuclear Translocator/genetics/*metabolismBreast Neoplasms/genetics/metabolism/pathologyCarcinoma, Hepatocellular/genetics/metabolism/pathologyCell LineCell Line, TransformedCell Line, TumorCell Transformation, ViralCurcumin/*pharmacologyCytochrome P-450 Enzyme System/*biosynthesisFemaleHumansHypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolismKidney/cytologyLiver Neoplasms/genetics/metabolism/pathologyMaleProstatic Neoplasms/genetics/metabolism/pathologyRNA, Small Interfering/metabolismReactive Oxygen Species/metabolismTetrachlorodibenzodioxin/*pharmacology
Abstract
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is a highly toxic environmental contaminant. When exposed to TCDD, mammalian cells undergo malignant transformation via abnormal intracellular signaling cascades, and the robust inductions of cytochrome P450 (CYP) enzymes are considered to mediate carcinogenesis by producing genotoxic metabolites. We here examined whether curcumin has preventive activity against TCDD-induced CYP production and cell transformation. Initially, the cellular levels of cytochrome P450 (CYP) 1A1 and 1B1 were examined, because these are known to generate estrogen metabolites that mediate genotoxic stress. Curcumin inhibited CYP1A1 and 1B1 induction by TCDD at the mRNA and protein levels. Notably, the nuclear levels of arylhydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT) were decreased by curcumin, but those in the cytoplasm were not. It was also found that oxidative stress mediated the curcumin-induced degradations of AhR and ARNT. Furthermore, in vitro transformation assays showed that in normal human embryonic kidney cells and normal prostate cells curcumin prevents the anchorage-independent growth induced by TCDD. In conclusion, curcumin attenuates AhR/ARNT-mediated CYP induction by dioxin and presumably this mode-of-action may be responsible for the curcumin prevention of malignant transformation. The findings of this study should be found helpful in the design stage of pharmacodynamic studies for developing curcumin as a chemopreventive or anticancer agent.
ISSN
1349-7006 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19018768

http://hdl.handle.net/10371/68123
DOI
https://doi.org/10.1111/j.1349-7006.2008.00984.x
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
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