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Title: Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity

Abstract

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 increased the expression and enzymatic activity of GST and QR. Moreover, FPP-3 increased transcriptional activity of GST and QR. GST and QR induction and Nrf2 translocation by FPP-3 were blocked by the PKC inhibitor Goe6983, and the p38 inhibitor SB203580. These results reflected a partial role of PKC{delta} and p38 signaling in FPP-3-mediated GSTA and QR induction through nuclear translocation of Nrf2. Classically, chemopreventive agents either inhibit CYP metabolizing enzyme or induce phase II detoxifying enzymes. These results suggest that FPP-3 hasmore » a potent protective effect against DMBA-induced genotoxicity through modulating phase I and II enzymes and that it has potential as a chemopreventive agent.« less

Authors:
; ; ; ;  [1]; ;  [2]
  1. BK21 Project Team, Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Gwangju (Korea, Republic of)
  2. College of Pharmacy, Yeungnam University, Kyungsan (Korea, Republic of)
Publication Date:
OSTI Identifier:
21140829
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 228; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2007.12.018; PII: S0041-008X(07)00577-7; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTHRACENE; ANTIOXIDANTS; ANTIPYRETICS; BENZOQUINONES; BIOLOGICAL STRESS; CARCINOGENS; DIMETHYLBENZANTHRACENE; DNA; ENZYME ACTIVITY; ENZYMES; FURANS; GENES; GLUTATHIONE; OXIDATION; RECEPTORS; TOXICITY; TRANSCRIPTION FACTORS; TRANSLOCATION

Citation Formats

Hwang, Yong Pil, Han, Eun Hee, Choi, Jae Ho, Kim, Hyung Gyun, Lee, Kyung Jin, Jeong, Tae Cheon, Lee, Eung Seok, and Jeong, Hye Gwang. Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity. United States: N. p., 2008. Web. doi:10.1016/j.taap.2007.12.018.
Hwang, Yong Pil, Han, Eun Hee, Choi, Jae Ho, Kim, Hyung Gyun, Lee, Kyung Jin, Jeong, Tae Cheon, Lee, Eung Seok, & Jeong, Hye Gwang. Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity. United States. https://doi.org/10.1016/j.taap.2007.12.018
Hwang, Yong Pil, Han, Eun Hee, Choi, Jae Ho, Kim, Hyung Gyun, Lee, Kyung Jin, Jeong, Tae Cheon, Lee, Eung Seok, and Jeong, Hye Gwang. 2008. "Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity". United States. https://doi.org/10.1016/j.taap.2007.12.018.
@article{osti_21140829,
title = {Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity},
author = {Hwang, Yong Pil and Han, Eun Hee and Choi, Jae Ho and Kim, Hyung Gyun and Lee, Kyung Jin and Jeong, Tae Cheon and Lee, Eung Seok and Jeong, Hye Gwang},
abstractNote = {1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 increased the expression and enzymatic activity of GST and QR. Moreover, FPP-3 increased transcriptional activity of GST and QR. GST and QR induction and Nrf2 translocation by FPP-3 were blocked by the PKC inhibitor Goe6983, and the p38 inhibitor SB203580. These results reflected a partial role of PKC{delta} and p38 signaling in FPP-3-mediated GSTA and QR induction through nuclear translocation of Nrf2. Classically, chemopreventive agents either inhibit CYP metabolizing enzyme or induce phase II detoxifying enzymes. These results suggest that FPP-3 has a potent protective effect against DMBA-induced genotoxicity through modulating phase I and II enzymes and that it has potential as a chemopreventive agent.},
doi = {10.1016/j.taap.2007.12.018},
url = {https://www.osti.gov/biblio/21140829}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 228,
place = {United States},
year = {Thu May 01 00:00:00 EDT 2008},
month = {Thu May 01 00:00:00 EDT 2008}
}