Differential effects of polycyclic aromatic hydrocarbons on transactivation of AP-1 and NF-κB in mouse epidermal Cl41 cells

Jingxia Li, Haobin Chen, Qingdong Ke, Zhaohui Feng, Moon Shong Tang, Bingci Liu, Shantu Amin, Max Costa, Chuanshu Huang

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Polycyclic aromatic hydrocarbons (PAHs) and their derivatives, such as benzo[a]pyrene (B[a]P), (±)-antibenzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), and 5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE), are complete carcinogens. However, the tumor promotion effects of PAHs remain unclear. We therefore investigated the possible activation of activator protein-1 (AP-1) and nuclear factor-κB (NFκB) in mouse epidermal Cl41 cells after different PAHs treatments, including B[a]P, B[a]PDE, chrysene-1,2-diol-3,4-epoxid (CDE), and 5-MCDE. The results showed that B[a]PDE and 5-MCDE were able to activate AP-1 and NF-κB, whereas B[a]P showed only marginal effect on AP-1 activation, and B[a]P and CDE had no effect on NF-κB activation. Treatment with either B[a]PDE or 5-MCDE also resulted in mitogen-activated protein kinases (MAPKs) activation as well as inhibitory subunit kappa-B (IκBα) phosphorylation and degradation, whereas B[a]P and CDE had no effect. Pretreatment with PD98059, a specific inhibitor for extracellular signal-regulated protein kinases (ERKs) upstream kinase MEK1/2, or SB202190, a p38 kinase inhibitor, resulted in a dramatic inhibition of B[a]PDE-induced AP-1 transactivation. In addition, B[a]PDE-induced AP-1 activation was also inhibited by overexpressing a dominant negative mutant of JNK1 in the cells. All these suggest ERKs, c-jun N-terminal kinases (JNKs), and p38 kinase signal transduction pathways are required for AP-1 induction by B[a]PDE. Taken together, B[a]PDE and 5-MCDE are the active compounds of PAHs to initiate signaling pathways. Considering the important roles of AP-1 and NF-κB in tumor promotion, we speculated the activation of AP-1 and NF-κB by B[a]PDE and 5-MCDE may involve in their or their parent compounds' tumor promotion effects. This study may help in better understanding the tumor promotion effects of PAHs.

Original languageEnglish (US)
Pages (from-to)104-115
Number of pages12
JournalMolecular Carcinogenesis
Volume40
Issue number2
DOIs
StatePublished - Jun 1 2004

Fingerprint

Polycyclic Aromatic Hydrocarbons
Transcription Factor AP-1
Transcriptional Activation
Benzo(a)pyrene
Phosphotransferases
Extracellular Signal-Regulated MAP Kinases
Protein Kinases
Neoplasms
JNK Mitogen-Activated Protein Kinases
Epoxy Compounds
Mitogen-Activated Protein Kinases
Carcinogens
1,2-dihydroxy-epoxy-1,2,3,4-tetrahydro-5-methylchrysene
Signal Transduction
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Cite this

Li, Jingxia ; Chen, Haobin ; Ke, Qingdong ; Feng, Zhaohui ; Tang, Moon Shong ; Liu, Bingci ; Amin, Shantu ; Costa, Max ; Huang, Chuanshu. / Differential effects of polycyclic aromatic hydrocarbons on transactivation of AP-1 and NF-κB in mouse epidermal Cl41 cells. In: Molecular Carcinogenesis. 2004 ; Vol. 40, No. 2. pp. 104-115.
@article{59de80d332d14566a29c49436eeede93,
title = "Differential effects of polycyclic aromatic hydrocarbons on transactivation of AP-1 and NF-κB in mouse epidermal Cl41 cells",
abstract = "Polycyclic aromatic hydrocarbons (PAHs) and their derivatives, such as benzo[a]pyrene (B[a]P), (±)-antibenzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), and 5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE), are complete carcinogens. However, the tumor promotion effects of PAHs remain unclear. We therefore investigated the possible activation of activator protein-1 (AP-1) and nuclear factor-κB (NFκB) in mouse epidermal Cl41 cells after different PAHs treatments, including B[a]P, B[a]PDE, chrysene-1,2-diol-3,4-epoxid (CDE), and 5-MCDE. The results showed that B[a]PDE and 5-MCDE were able to activate AP-1 and NF-κB, whereas B[a]P showed only marginal effect on AP-1 activation, and B[a]P and CDE had no effect on NF-κB activation. Treatment with either B[a]PDE or 5-MCDE also resulted in mitogen-activated protein kinases (MAPKs) activation as well as inhibitory subunit kappa-B (IκBα) phosphorylation and degradation, whereas B[a]P and CDE had no effect. Pretreatment with PD98059, a specific inhibitor for extracellular signal-regulated protein kinases (ERKs) upstream kinase MEK1/2, or SB202190, a p38 kinase inhibitor, resulted in a dramatic inhibition of B[a]PDE-induced AP-1 transactivation. In addition, B[a]PDE-induced AP-1 activation was also inhibited by overexpressing a dominant negative mutant of JNK1 in the cells. All these suggest ERKs, c-jun N-terminal kinases (JNKs), and p38 kinase signal transduction pathways are required for AP-1 induction by B[a]PDE. Taken together, B[a]PDE and 5-MCDE are the active compounds of PAHs to initiate signaling pathways. Considering the important roles of AP-1 and NF-κB in tumor promotion, we speculated the activation of AP-1 and NF-κB by B[a]PDE and 5-MCDE may involve in their or their parent compounds' tumor promotion effects. This study may help in better understanding the tumor promotion effects of PAHs.",
author = "Jingxia Li and Haobin Chen and Qingdong Ke and Zhaohui Feng and Tang, {Moon Shong} and Bingci Liu and Shantu Amin and Max Costa and Chuanshu Huang",
year = "2004",
month = "6",
day = "1",
doi = "10.1002/mc.20020",
language = "English (US)",
volume = "40",
pages = "104--115",
journal = "Molecular Carcinogenesis",
issn = "0899-1987",
publisher = "Wiley-Liss Inc.",
number = "2",

}

Differential effects of polycyclic aromatic hydrocarbons on transactivation of AP-1 and NF-κB in mouse epidermal Cl41 cells. / Li, Jingxia; Chen, Haobin; Ke, Qingdong; Feng, Zhaohui; Tang, Moon Shong; Liu, Bingci; Amin, Shantu; Costa, Max; Huang, Chuanshu.

In: Molecular Carcinogenesis, Vol. 40, No. 2, 01.06.2004, p. 104-115.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Differential effects of polycyclic aromatic hydrocarbons on transactivation of AP-1 and NF-κB in mouse epidermal Cl41 cells

AU - Li, Jingxia

AU - Chen, Haobin

AU - Ke, Qingdong

AU - Feng, Zhaohui

AU - Tang, Moon Shong

AU - Liu, Bingci

AU - Amin, Shantu

AU - Costa, Max

AU - Huang, Chuanshu

PY - 2004/6/1

Y1 - 2004/6/1

N2 - Polycyclic aromatic hydrocarbons (PAHs) and their derivatives, such as benzo[a]pyrene (B[a]P), (±)-antibenzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), and 5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE), are complete carcinogens. However, the tumor promotion effects of PAHs remain unclear. We therefore investigated the possible activation of activator protein-1 (AP-1) and nuclear factor-κB (NFκB) in mouse epidermal Cl41 cells after different PAHs treatments, including B[a]P, B[a]PDE, chrysene-1,2-diol-3,4-epoxid (CDE), and 5-MCDE. The results showed that B[a]PDE and 5-MCDE were able to activate AP-1 and NF-κB, whereas B[a]P showed only marginal effect on AP-1 activation, and B[a]P and CDE had no effect on NF-κB activation. Treatment with either B[a]PDE or 5-MCDE also resulted in mitogen-activated protein kinases (MAPKs) activation as well as inhibitory subunit kappa-B (IκBα) phosphorylation and degradation, whereas B[a]P and CDE had no effect. Pretreatment with PD98059, a specific inhibitor for extracellular signal-regulated protein kinases (ERKs) upstream kinase MEK1/2, or SB202190, a p38 kinase inhibitor, resulted in a dramatic inhibition of B[a]PDE-induced AP-1 transactivation. In addition, B[a]PDE-induced AP-1 activation was also inhibited by overexpressing a dominant negative mutant of JNK1 in the cells. All these suggest ERKs, c-jun N-terminal kinases (JNKs), and p38 kinase signal transduction pathways are required for AP-1 induction by B[a]PDE. Taken together, B[a]PDE and 5-MCDE are the active compounds of PAHs to initiate signaling pathways. Considering the important roles of AP-1 and NF-κB in tumor promotion, we speculated the activation of AP-1 and NF-κB by B[a]PDE and 5-MCDE may involve in their or their parent compounds' tumor promotion effects. This study may help in better understanding the tumor promotion effects of PAHs.

AB - Polycyclic aromatic hydrocarbons (PAHs) and their derivatives, such as benzo[a]pyrene (B[a]P), (±)-antibenzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), and 5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE), are complete carcinogens. However, the tumor promotion effects of PAHs remain unclear. We therefore investigated the possible activation of activator protein-1 (AP-1) and nuclear factor-κB (NFκB) in mouse epidermal Cl41 cells after different PAHs treatments, including B[a]P, B[a]PDE, chrysene-1,2-diol-3,4-epoxid (CDE), and 5-MCDE. The results showed that B[a]PDE and 5-MCDE were able to activate AP-1 and NF-κB, whereas B[a]P showed only marginal effect on AP-1 activation, and B[a]P and CDE had no effect on NF-κB activation. Treatment with either B[a]PDE or 5-MCDE also resulted in mitogen-activated protein kinases (MAPKs) activation as well as inhibitory subunit kappa-B (IκBα) phosphorylation and degradation, whereas B[a]P and CDE had no effect. Pretreatment with PD98059, a specific inhibitor for extracellular signal-regulated protein kinases (ERKs) upstream kinase MEK1/2, or SB202190, a p38 kinase inhibitor, resulted in a dramatic inhibition of B[a]PDE-induced AP-1 transactivation. In addition, B[a]PDE-induced AP-1 activation was also inhibited by overexpressing a dominant negative mutant of JNK1 in the cells. All these suggest ERKs, c-jun N-terminal kinases (JNKs), and p38 kinase signal transduction pathways are required for AP-1 induction by B[a]PDE. Taken together, B[a]PDE and 5-MCDE are the active compounds of PAHs to initiate signaling pathways. Considering the important roles of AP-1 and NF-κB in tumor promotion, we speculated the activation of AP-1 and NF-κB by B[a]PDE and 5-MCDE may involve in their or their parent compounds' tumor promotion effects. This study may help in better understanding the tumor promotion effects of PAHs.

UR - http://www.scopus.com/inward/record.url?scp=2942620289&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942620289&partnerID=8YFLogxK

U2 - 10.1002/mc.20020

DO - 10.1002/mc.20020

M3 - Article

C2 - 15170815

AN - SCOPUS:2942620289

VL - 40

SP - 104

EP - 115

JO - Molecular Carcinogenesis

JF - Molecular Carcinogenesis

SN - 0899-1987

IS - 2

ER -