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

https://doi.org/10.1016/j.bbamcr.2017.06.017 Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Quercetin inhibits the migration/invasion of NSCLC cells through suppressing the EMT.

  • Quercetin attenuates bone metastasis and prolongs lifespan in an in vivo model.

  • Quercetin suppresses snail-dependent Akt activation by upregulating maspin.

  • Quercetin suppresses snail-independent ADAM9 expression.

  • Snail or ADAM9 expression is inversely correlated with survival of patients.

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.

Abbreviations

ADC
adenocarcinoma
ADAM9
a disintegrin and metalloprotease 9
EMT
epithelial-to-mesenchymal transition
ECM
extracellular matrix
IHC
immunohistochemical
MMP
matrix metalloproteinase
PTEN
phosphatase and tensin homologue
GSH
glutathione
NSCLC
non-small cell lung cancer
uPA
urokinase plasminogen activator

Keywords

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

Cited by (0)

1

Jer-Hwa Chang and Shu-Leung Lai contributed equally to this work.