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Acetaldehyde induces matrix metalloproteinase-9 gene expression via nuclear factor-kappaB and activator protein 1 signaling pathways in human hepatocellular carcinoma cells: Association with the invasive potential.
Toxicol Lett. 2007 Jun 15; 171(1-2):78-86.TL

Abstract

Alcohol consumption is a significant risk factor for hepatocellular carcinoma (HCC). Alcohol also increases the prevalence of invasion in HCC patients. However, the molecular mechanism on the metastatic effect of alcohol is unclear so far. Herein we demonstrated that acetaldehyde, the primary metabolite of ethanol, increased matrix metalloproteinase-9 (MMP-9) gelatinolytic activity and promoted cell invasion through the up-regulation of MMP-9 gene transcription in HepG2 cells. The transcription of MMP-9 gene was regulated by 10 microM acetaldehyde via inductions of nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) activities. Acetaldehyde stimulated the translocation of NF-kappaB into nucleus through inhibitory kappaB-alpha (IkappaB-alpha) and c-Jun N-terminal kinase (JNK)/beta-transducin repeat-containing protein (beta-TrCP) signaling pathways. Acetaldehyde also induced AP-1 activity via the phosphorylation of p38 kinase. In conclusion, our findings demonstrated for the first time that acetaldehyde activated NF-kappaB and AP-1 activities via IkappaB, JNK/beta-TrCP, and p38 signaling pathways, resulting in MMP-9 gene expression and hepatocarcinoma cells invasion. These results suggested that acetaldehyde might be a potential factor involved in the invasiveness of HCC in alcoholic patients.

Authors+Show Affiliations

Department of Microbiology, China Medical University, Taichung 40402, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17543481

Citation

Hsiang, Chien-Yun, et al. "Acetaldehyde Induces Matrix Metalloproteinase-9 Gene Expression Via Nuclear factor-kappaB and Activator Protein 1 Signaling Pathways in Human Hepatocellular Carcinoma Cells: Association With the Invasive Potential." Toxicology Letters, vol. 171, no. 1-2, 2007, pp. 78-86.
Hsiang CY, Wu SL, Chen JC, et al. Acetaldehyde induces matrix metalloproteinase-9 gene expression via nuclear factor-kappaB and activator protein 1 signaling pathways in human hepatocellular carcinoma cells: Association with the invasive potential. Toxicol Lett. 2007;171(1-2):78-86.
Hsiang, C. Y., Wu, S. L., Chen, J. C., Lo, H. Y., Li, C. C., Chiang, S. Y., Wu, H. C., & Ho, T. Y. (2007). Acetaldehyde induces matrix metalloproteinase-9 gene expression via nuclear factor-kappaB and activator protein 1 signaling pathways in human hepatocellular carcinoma cells: Association with the invasive potential. Toxicology Letters, 171(1-2), 78-86.
Hsiang CY, et al. Acetaldehyde Induces Matrix Metalloproteinase-9 Gene Expression Via Nuclear factor-kappaB and Activator Protein 1 Signaling Pathways in Human Hepatocellular Carcinoma Cells: Association With the Invasive Potential. Toxicol Lett. 2007 Jun 15;171(1-2):78-86. PubMed PMID: 17543481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acetaldehyde induces matrix metalloproteinase-9 gene expression via nuclear factor-kappaB and activator protein 1 signaling pathways in human hepatocellular carcinoma cells: Association with the invasive potential. AU - Hsiang,Chien-Yun, AU - Wu,Shih-Lu, AU - Chen,Jaw-Chyun, AU - Lo,Hsin-Yi, AU - Li,Chia-Cheng, AU - Chiang,Su-Yin, AU - Wu,Hsiu-Ching, AU - Ho,Tin-Yun, Y1 - 2007/04/27/ PY - 2007/02/07/received PY - 2007/04/23/revised PY - 2007/04/24/accepted PY - 2007/6/5/pubmed PY - 2007/9/21/medline PY - 2007/6/5/entrez SP - 78 EP - 86 JF - Toxicology letters JO - Toxicol Lett VL - 171 IS - 1-2 N2 - Alcohol consumption is a significant risk factor for hepatocellular carcinoma (HCC). Alcohol also increases the prevalence of invasion in HCC patients. However, the molecular mechanism on the metastatic effect of alcohol is unclear so far. Herein we demonstrated that acetaldehyde, the primary metabolite of ethanol, increased matrix metalloproteinase-9 (MMP-9) gelatinolytic activity and promoted cell invasion through the up-regulation of MMP-9 gene transcription in HepG2 cells. The transcription of MMP-9 gene was regulated by 10 microM acetaldehyde via inductions of nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) activities. Acetaldehyde stimulated the translocation of NF-kappaB into nucleus through inhibitory kappaB-alpha (IkappaB-alpha) and c-Jun N-terminal kinase (JNK)/beta-transducin repeat-containing protein (beta-TrCP) signaling pathways. Acetaldehyde also induced AP-1 activity via the phosphorylation of p38 kinase. In conclusion, our findings demonstrated for the first time that acetaldehyde activated NF-kappaB and AP-1 activities via IkappaB, JNK/beta-TrCP, and p38 signaling pathways, resulting in MMP-9 gene expression and hepatocarcinoma cells invasion. These results suggested that acetaldehyde might be a potential factor involved in the invasiveness of HCC in alcoholic patients. SN - 0378-4274 UR - https://www.unboundmedicine.com/medline/citation/17543481/Acetaldehyde_induces_matrix_metalloproteinase_9_gene_expression_via_nuclear_factor_kappaB_and_activator_protein_1_signaling_pathways_in_human_hepatocellular_carcinoma_cells:_Association_with_the_invasive_potential_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(07)00126-9 DB - PRIME DP - Unbound Medicine ER -