Quercetin suppresses the metastatic ability of lung cancer through inhibiting Snail-dependent Akt activation and Snail-independent ADAM9 expression pathways

Jer Hwa Chang, Shu Leung Lai, Wan Shen Chen, Wen Yueh Hung, Jyh Ming Chow, Michael Hsiao, Wei Jiunn Lee, Ming Hsien Chien

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Metastasis is the major cause of death from lung cancer. Quercetin, a widely distributed bioflavonoid, is well known to induce growth inhibition in a variety of human cancer cells, but how it affects lung cancer cell invasion and metastasis is unclear. Herein, we found that quercetin inhibited the migration/invasion of non-small cell lung cancer (NSCLC) cell lines and bone metastasis in an orthotopic A549 xenograft model by suppressing the Snail-mediated epithelial-to-mesenchymal transition (EMT). Moreover, survival times of animals were also prolonged after quercetin treatment. Mechanistic investigations found that quercetin suppressed Snail-dependent Akt activation by upregulating maspin and Snail-independent a disintegrin and metalloproteinase (ADAM) 9 expression pathways to modulate the invasive ability of NSCLC cells. In clinical samples, we observed that patients with Snailhigh/p-Akthigh tumors had the shortest survival times. In addition, a lower survival rate was also found in ADAM9high patients than in ADAM9low patients. Overall, our results provide new insights into the role of quercetin-induced molecular regulation in suppressing NSCLC metastasis and suggest that quercetin has potential therapeutic applications for metastatic NSCLC.

Original languageEnglish
Pages (from-to)1746-1758
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1864
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

Keywords

  • A disintegrin and metalloprotease 9
  • Akt
  • Invasion
  • Non-small cell lung cancer
  • Quercetin
  • Snail

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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