In vitro enhancement effect of humic acid on the progression of lung cancer cells

Wei Jiunn Lee, Fung Jou Lu, Shan Fu Wang, Yun Ru Chen, Tsui Hwa Tseng

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Humic acid, a group of polymer, resulting from the decomposition of organic matter has been implicated as a possible etiological factor for Black foot disease and cancer. However, the role of humic acid in carcinogenesis is not well clarified. In this study, we evaluated the enhancement effect of humic acid on the progression of A549 human lung cancer cells. Our findings showed that humic acid increased the migration, adhesion and invasion of A549 cells significantly after treatment at the concentration of 50 and 100 μg/ml for 24 and 48 h as compared with the untreated group. Results of zymography assay indicated that humic acid enhanced the activity of matrix metalloproteinase 9 (MMP-9). By western blotting analysis, humic acid increased the expression of phosphorylated focal adhesion kinase (FAK) and integrin α2 that may mediate cell motility and adhesion. Since the activation of signal pathways such as phosphoinositide 3-kinase/Akt (PI3K/Akt) and mitogen-activated protein kinases (MAPKs) may play a role in the cell invasion, we detected the expression of phosphorylated Akt and phosphorylated MAPKs including extracellular signal-regulated kinase (ERK), Jun N-terminus kinase (JNK), and p38. The result indicated that all kinases stated above were activated by humic acid in A549 cells. However, by adding an inhibitor respectively in the invasion assay, only Akt, ERK, and JNK pathways were found to be involved in the enhancing the invasion of A549 cells by humic acid. In addition, results of electrophoretic mobility shift assay (EMSA) demonstrated that humic acid increased nuclear extract binding to the DNA probe of activator protein 1 (AP-1) and nuclear factor κB (NFκB) respectively, implying that humic acid enhanced the progression of A549 lung cancer cells through activating multiple signaling pathways including ERK, JNK, and PI3K/Akt and increasing the transcription activation of AP-1 and NFκB.

Original languageEnglish
Pages (from-to)463-471
Number of pages9
JournalChemico-Biological Interactions
Volume181
Issue number3
DOIs
Publication statusPublished - Oct 30 2009
Externally publishedYes

Fingerprint

Humic Substances
Lung Neoplasms
Cells
Phosphotransferases
Extracellular Signal-Regulated MAP Kinases
Assays
1-Phosphatidylinositol 4-Kinase
Transcription Factor AP-1
Mitogen-Activated Protein Kinases
Focal Adhesion Kinase 2
Adhesion
Foot Diseases
Chemical activation
In Vitro Techniques
Focal Adhesion Protein-Tyrosine Kinases
Electrophoretic mobility
Matrix Metalloproteinase 9
DNA Probes
Electrophoretic Mobility Shift Assay
Transcription

Keywords

  • Humic acid
  • Progression
  • Signaling pathways

ASJC Scopus subject areas

  • Toxicology

Cite this

In vitro enhancement effect of humic acid on the progression of lung cancer cells. / Lee, Wei Jiunn; Lu, Fung Jou; Wang, Shan Fu; Chen, Yun Ru; Tseng, Tsui Hwa.

In: Chemico-Biological Interactions, Vol. 181, No. 3, 30.10.2009, p. 463-471.

Research output: Contribution to journalArticle

Lee, Wei Jiunn ; Lu, Fung Jou ; Wang, Shan Fu ; Chen, Yun Ru ; Tseng, Tsui Hwa. / In vitro enhancement effect of humic acid on the progression of lung cancer cells. In: Chemico-Biological Interactions. 2009 ; Vol. 181, No. 3. pp. 463-471.
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