Arecoline Promotes Migration of A549 Lung Cancer Cells through Activating the EGFR/Src/FAK Pathway

Chih Hsiang Chang, Mei Chih Chen, Te Huan Chiu, Yu Hsuan Li, Wan Chen Yu, Wan Ling Liao, Muhammet Oner, Chang Tze Ricky Yu, Chun Chi Wu, Tsung Ying Yang, Chieh Lin Jerry Teng, Kun Yuan Chiu, Kun Chien Chen, Hsin Yi Wang, Chia Herng Yue, Chih Ho Lai, Jer-Tsong Hsieh, Ho Lin

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Arecoline is the primary alkaloid in betel nuts, which are known as a risk factor for oral submucosal fibrosis and oral cancer. Lung cancer is a severe type of carcinoma with high cell motility that is difficult to treat. However, the detailed mechanisms of the correlation between Arecoline and lung cancer are not fully understood. Here, we investigated the effect of Arecoline on migration in lung cancer cell lines and its potential mechanism through the muscarinic acetylcholine receptor 3 (mAChR3)-triggered EGFR/Src/FAK pathway. Our results indicate that different concentrations of Arecoline treatment (10 µM, 20 µM, and 40 µM) significantly increased the cell migration ability in A549 and CL1-0 cells and promoted the formation of the filamentous actin (F-actin) cytoskeleton, which is a crucial element for cell migration. However, migration of H460, CL1-5, and H520 cell lines, which have a higher migration ability, was not affected by Arecoline treatment. The EGFR/c-Src/Fak pathway, which is responsible for cell migration, was activated by Arecoline treatment, and a decreased expression level of E-cadherin, which is an epithelial marker, was observed in Arecoline-treated cell lines. Blockade of the EGFR/c-Src/Fak pathway with the inhibitors of EGFR (Gefitinib) or c-Src (Dasatinib) significantly prevented Arecoline-promoted migration in A549 cells. Gefitinib or Dasatinib treatment significantly disrupted the Arecoline-induced localization of phospho-Y576-Fak during focal adhesion in A549 cells. Interestingly, Arecoline-promoted migration in A549 cells was blocked by a specific mAChR3 inhibitor (4-DAMP) or a neutralizing antibody of matrix metalloproteinase (MMP7 or Matrilysin). Taken together, our findings suggest that mAChR3 might play an essential role in Arecoline-promoted EGFR/c-Src/Fak activation and migration in an A549 lung cancer cell line.

Original languageEnglish (US)
JournalToxins
Volume11
Issue number4
DOIs
StatePublished - Mar 28 2019

Fingerprint

Arecoline
Lung Neoplasms
Cells
Cell Movement
Muscarinic Receptors
Cell Line
Areca
Matrix Metalloproteinase 7
Focal Adhesions
Mouth Neoplasms
Cadherins
Neutralizing Antibodies
Matrix Metalloproteinases
Actin Cytoskeleton
Alkaloids
Actins

Keywords

  • Arecoline
  • EGFR
  • FAK
  • lung cancer cells
  • mAchR3
  • SRC

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Chang, C. H., Chen, M. C., Chiu, T. H., Li, Y. H., Yu, W. C., Liao, W. L., ... Lin, H. (2019). Arecoline Promotes Migration of A549 Lung Cancer Cells through Activating the EGFR/Src/FAK Pathway. Toxins, 11(4). https://doi.org/10.3390/toxins11040185

Arecoline Promotes Migration of A549 Lung Cancer Cells through Activating the EGFR/Src/FAK Pathway. / Chang, Chih Hsiang; Chen, Mei Chih; Chiu, Te Huan; Li, Yu Hsuan; Yu, Wan Chen; Liao, Wan Ling; Oner, Muhammet; Yu, Chang Tze Ricky; Wu, Chun Chi; Yang, Tsung Ying; Teng, Chieh Lin Jerry; Chiu, Kun Yuan; Chen, Kun Chien; Wang, Hsin Yi; Yue, Chia Herng; Lai, Chih Ho; Hsieh, Jer-Tsong; Lin, Ho.

In: Toxins, Vol. 11, No. 4, 28.03.2019.

Research output: Contribution to journalArticle

Chang, CH, Chen, MC, Chiu, TH, Li, YH, Yu, WC, Liao, WL, Oner, M, Yu, CTR, Wu, CC, Yang, TY, Teng, CLJ, Chiu, KY, Chen, KC, Wang, HY, Yue, CH, Lai, CH, Hsieh, J-T & Lin, H 2019, 'Arecoline Promotes Migration of A549 Lung Cancer Cells through Activating the EGFR/Src/FAK Pathway', Toxins, vol. 11, no. 4. https://doi.org/10.3390/toxins11040185
Chang, Chih Hsiang ; Chen, Mei Chih ; Chiu, Te Huan ; Li, Yu Hsuan ; Yu, Wan Chen ; Liao, Wan Ling ; Oner, Muhammet ; Yu, Chang Tze Ricky ; Wu, Chun Chi ; Yang, Tsung Ying ; Teng, Chieh Lin Jerry ; Chiu, Kun Yuan ; Chen, Kun Chien ; Wang, Hsin Yi ; Yue, Chia Herng ; Lai, Chih Ho ; Hsieh, Jer-Tsong ; Lin, Ho. / Arecoline Promotes Migration of A549 Lung Cancer Cells through Activating the EGFR/Src/FAK Pathway. In: Toxins. 2019 ; Vol. 11, No. 4.
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AU - Chen, Mei Chih

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AU - Li, Yu Hsuan

AU - Yu, Wan Chen

AU - Liao, Wan Ling

AU - Oner, Muhammet

AU - Yu, Chang Tze Ricky

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AU - Teng, Chieh Lin Jerry

AU - Chiu, Kun Yuan

AU - Chen, Kun Chien

AU - Wang, Hsin Yi

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