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Title: Induction of COX-2 protein expression by vanadate in A549 human lung carcinoma cell line through EGF receptor and p38 MAPK-mediated pathway

Abstract

Vanadate is a transition metal widely distributed in the environment. It has been reported that vanadate associated with air pollution particles can modify DNA synthesis, causing cell growth arrest, and apoptosis. Moreover, vanadium exposure was also found to cause the synthesis of inflammatory cytokines, such as interleukin-1, tumor necrosis factor-{alpha}, and prostaglandin E{sub 2}. Here, we found that exposure of A549 human lung carcinoma cells to vanadate led to extracellular signal-regulated kinase, c-Jun NH{sub 2}-terminal protein kinases (JNKs), p38 mitogen-activated protein kinase (p38) activation, and COX-2 protein expression in a dose-dependent manner. SB203580, a p38 MAPK inhibitor, but not PD098059 and SP600125, specific inhibitor of MKK1 and selective inhibitor of JNK, respectively, suppressed COX-2 expression. Furthermore, the epithelial growth factor (EGF) receptor specific inhibitor (PD153035) reduced vanadate-induced COX-2 expression. However, scavenging of vanadate-induced reactive oxygen species by catalase, a specific H{sub 2}O{sub 2} inhibitor, or DPI, an NADPH oxidase inhibitor, resulted in no inhibition on COX-2 expression. Together, we suggested that EGF receptor and p38 MAPK signaling pathway may be involved in vanadate-induced COX-2 protein expression in A549 human lung carcinoma cell line.

Authors:
 [1];  [1];  [2];  [3]
  1. Institute of Biotechnology, National Cheng Kung University, No. 1 University Rd. 701, Tainan, Taiwan (China)
  2. (China)
  3. Institute of Biotechnology, National Cheng Kung University, No. 1 University Rd. 701, Tainan, Taiwan (China) and Department of Life Sciences, National Cheng Kung University, No. 1 University Rd. 701, Tainan, Taiwan (China). E-mail: haojen@mail.ncku.edu.tw
Publication Date:
OSTI Identifier:
20798745
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 339; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2005.11.045; PII: S0006-291X(05)02540-4; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIR POLLUTION; APOPTOSIS; BIOSYNTHESIS; CARCINOMAS; CATALASE; DNA; HYDROGEN PEROXIDE; INFLAMMATION; INHIBITION; LUNGS; LYMPHOKINES; OXIDASES; PHOSPHOTRANSFERASES; PROSTAGLANDINS; RECEPTORS; VANADIUM

Citation Formats

Chien, P.-S., Mak, O.-T., Department of Life Sciences, National Cheng Kung University, No. 1 University Rd. 701, Tainan, Taiwan, and Huang, H.-J.. Induction of COX-2 protein expression by vanadate in A549 human lung carcinoma cell line through EGF receptor and p38 MAPK-mediated pathway. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2005.11.045.
Chien, P.-S., Mak, O.-T., Department of Life Sciences, National Cheng Kung University, No. 1 University Rd. 701, Tainan, Taiwan, & Huang, H.-J.. Induction of COX-2 protein expression by vanadate in A549 human lung carcinoma cell line through EGF receptor and p38 MAPK-mediated pathway. United States. doi:10.1016/j.bbrc.2005.11.045.
Chien, P.-S., Mak, O.-T., Department of Life Sciences, National Cheng Kung University, No. 1 University Rd. 701, Tainan, Taiwan, and Huang, H.-J.. Fri . "Induction of COX-2 protein expression by vanadate in A549 human lung carcinoma cell line through EGF receptor and p38 MAPK-mediated pathway". United States. doi:10.1016/j.bbrc.2005.11.045.
@article{osti_20798745,
title = {Induction of COX-2 protein expression by vanadate in A549 human lung carcinoma cell line through EGF receptor and p38 MAPK-mediated pathway},
author = {Chien, P.-S. and Mak, O.-T. and Department of Life Sciences, National Cheng Kung University, No. 1 University Rd. 701, Tainan, Taiwan and Huang, H.-J.},
abstractNote = {Vanadate is a transition metal widely distributed in the environment. It has been reported that vanadate associated with air pollution particles can modify DNA synthesis, causing cell growth arrest, and apoptosis. Moreover, vanadium exposure was also found to cause the synthesis of inflammatory cytokines, such as interleukin-1, tumor necrosis factor-{alpha}, and prostaglandin E{sub 2}. Here, we found that exposure of A549 human lung carcinoma cells to vanadate led to extracellular signal-regulated kinase, c-Jun NH{sub 2}-terminal protein kinases (JNKs), p38 mitogen-activated protein kinase (p38) activation, and COX-2 protein expression in a dose-dependent manner. SB203580, a p38 MAPK inhibitor, but not PD098059 and SP600125, specific inhibitor of MKK1 and selective inhibitor of JNK, respectively, suppressed COX-2 expression. Furthermore, the epithelial growth factor (EGF) receptor specific inhibitor (PD153035) reduced vanadate-induced COX-2 expression. However, scavenging of vanadate-induced reactive oxygen species by catalase, a specific H{sub 2}O{sub 2} inhibitor, or DPI, an NADPH oxidase inhibitor, resulted in no inhibition on COX-2 expression. Together, we suggested that EGF receptor and p38 MAPK signaling pathway may be involved in vanadate-induced COX-2 protein expression in A549 human lung carcinoma cell line.},
doi = {10.1016/j.bbrc.2005.11.045},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 339,
place = {United States},
year = {Fri Jan 13 00:00:00 EST 2006},
month = {Fri Jan 13 00:00:00 EST 2006}
}
  • Rad51 is an essential component of the homologous recombination repair pathway. Abnormal expression of Rad51 has been reported in various carcinomas. Benzo[a]pyrene (B[a]P), a polycyclic hydrocarbon carcinogen found in the environment, induces cancer in multiple organs. B[a]P has been shown to activate the p38 MAPK signaling pathway in mammalian cells. The prime purpose of this study was to determine how B[a]P activates the p38 MAPK signaling pathway, and how this then regulates Rad51 expression in human cancer cells. Exposure of human lung cancer cells with B[a]P increased Rad51 protein levels in a time- and dose-dependent fashion. B[a]P also induced Rad51more » mRNA and protein synthesis. Blockage of p38 MAPK activation by SB202190 or small interfering RNA (si-p38) decreased B[a]P-elicited Rad51 protein levels by increasing Rad51 protein instability, but did not affect Rad51 mRNA transcription. Furthermore, enhancement of p38 MAPK signaling by constitutively active MKK6 (MKK6E) increased Rad51 protein levels and protein stability. Moreover, B[a]P-induced cytotoxicity and mutagenicity were significantly increased in cells depleted of endogenous Rad51. Taken together, these results indicate that Rad51 protein provides a critical role in inhibiting the cytotoxicity and mutagenicity of B[a]P in B[a]P-treated human lung cancer cells. Furthermore, the work points to an unexpected role of p38 MAPK signaling in the control of Rad51 protein stability in response to B[a]P exposure.« less
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  • Purpose: To investigate the mechanism of interleukin-6 (IL-6) activity induced by ionizing radiation. Methods and Materials: Human umbilical vascular endothelial cells (HUVECs) were irradiated with different doses to induce IL-6. The IL-6 promoter assay and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to examine transcriptional regulation. Specific chemical inhibitors, decoy double-stranded oligodeoxynucleotides, and Western blotting were conducted to investigate the signal transduction pathway. Recombinant soluble human IL-6 receptor alpha-chain (sIL6-Ralpha) and specific small interfering RNA were used to evaluate the biologic function of radiation-induced IL-6. Results: Four grays of radiation induced the highest level of IL-6 protein. The promoter assaymore » and RT-PCR data revealed that the induction of IL-6 was mediated through transcriptional regulation. The p38 inhibitor SB203580, by blocking nuclear factor-kappaB (NF-kappaB) activation, prevented both the transcriptional and translational regulation of radiation-induced IL-6 expression. The addition of sIL6-Ralpha rescued HUVECs from radiation-induced death in an IL-6 concentratio-dependent manner. The antiapoptotic effect of combined sIL6-Ralpha and radiation-induced IL-6 was inhibited by mcl-1-specific small interfering RNA. Conclusion: Radiation transcriptionally induces IL-6 expression in endothelial cells through mitogen-activated protein kinase/p38-mediated NF-kappaB/IkappaB (inhibitor of NF-kappaB) complex activation. In the presence of sIL6-Ralpha, radiation-induced IL-6 expression acts through Mcl-1 expression to rescue endothelial cells from radiation-induced death.« less