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

研究成果: 雜誌貢獻文章

11 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)1746-1758
頁數13
期刊Biochimica et Biophysica Acta - Molecular Cell Research
1864
發行號10
DOIs
出版狀態已發佈 - 十月 1 2017

指紋

Quercetin
Lung Neoplasms
Non-Small Cell Lung Carcinoma
Neoplasm Metastasis
Disintegrins
Epithelial-Mesenchymal Transition
Survival
Metalloproteases
Flavonoids
Heterografts
Cause of Death
Neoplasms
Survival Rate
Bone and Bones
Cell Line
Therapeutics
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

引用此文

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title = "Quercetin suppresses the metastatic ability of lung cancer through inhibiting Snail-dependent Akt activation and Snail-independent ADAM9 expression pathways",
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.",
keywords = "A disintegrin and metalloprotease 9, Akt, Invasion, Non-small cell lung cancer, Quercetin, Snail",
author = "Chang, {Jer Hwa} and Lai, {Shu Leung} and Chen, {Wan Shen} and Hung, {Wen Yueh} and Chow, {Jyh Ming} and Michael Hsiao and Lee, {Wei Jiunn} and Chien, {Ming Hsien}",
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T1 - Quercetin suppresses the metastatic ability of lung cancer through inhibiting Snail-dependent Akt activation and Snail-independent ADAM9 expression pathways

AU - Chang, Jer Hwa

AU - Lai, Shu Leung

AU - Chen, Wan Shen

AU - Hung, Wen Yueh

AU - Chow, Jyh Ming

AU - Hsiao, Michael

AU - Lee, Wei Jiunn

AU - Chien, Ming Hsien

PY - 2017/10/1

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AB - 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.

KW - A disintegrin and metalloprotease 9

KW - Akt

KW - Invasion

KW - Non-small cell lung cancer

KW - Quercetin

KW - Snail

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