Nutr Res Pract.  2020 Apr;14(2):127-133. 10.4162/nrp.2020.14.2.127.

Luteolin attenuates migration and invasion of lung cancer cells via suppressing focal adhesion kinase and non-receptor tyrosine kinase signaling pathway

Affiliations
  • 1Department of Pharmacology, Faculty of Science, Prince of Songkla University, Songkhla, 90110, Thailand. wanida.su@psu.ac.th
  • 2Department of Anatomy, Faculty of Science, Prince of Songkla University, Songkhla, 90110, Thailand.
  • 3Department of Physiology, Faculty of Science, Prince of Songkla University, Songkhla, 90110, Thailand.

Abstract

BACKGROUND/OBJECTIVES
Non-small cell lung cancer is mostly recognized among other types of lung cancer with a poor prognosis by cause of chemotherapeutic resistance and increased metastasis. Luteolin has been found to decrease cell metastasis. However, its underlying mechanisms remain unresolved. The objective of this study was to examine the effect (and its mechanism) of luteolin on the migration and invasion of human non-small cell lung cancer A549 cells.
MATERIALS/METHODS
Cell viability was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing and transwell assays were evaluated to assess migration and invasion, respectively. Western blot analysis and immunofluorescence were further performed to investigate the role of luteolin and its mechanisms of action.
RESULTS
Administration with up to 40 µM luteolin showed no cytotoxic activity on lung cancer A549 cells or non-cancer MRC-5 cells. Additionally, luteolin at 20-40 µM significantly suppressed A549 cells' migration, invasion, and the formation of filopodia in a concentration-dependent manner at 24 h. This is similar with western blot analysis, which revealed diminished the phosphorylated focal adhesion kinase (pFAK), phosphorylated non-receptor tyrosine kinase (pSrc), Ras-related C3 botulinum toxin substrate 1 (Rac1), cell division control protein 42 (Cdc42), and Ras homolog gene family member A (RhoA) expression levels.
CONCLUSIONS
Overall, our data indicate that luteolin plays a role in controlling lung cancer cells' migration and invasion via Src/FAK and its downstream Rac1, Cdc42, and RhoA pathways. Luteolin might be considered a promising candidate for suppressing invasion and metastasis of lung cancer cells.

Keyword

Adenocarcinoma; flavonoids; luteolin; A549 cell

MeSH Terms

Adenocarcinoma
Blotting, Western
Carcinoma, Non-Small-Cell Lung
Cell Division
Cell Survival
Flavonoids
Fluorescent Antibody Technique
Focal Adhesion Protein-Tyrosine Kinases*
Focal Adhesions*
Humans
Lung Neoplasms*
Lung*
Luteolin*
Neoplasm Metastasis
Prognosis
Protein-Tyrosine Kinases*
Pseudopodia
rac1 GTP-Binding Protein
Tyrosine*
Wound Healing
Flavonoids
Focal Adhesion Protein-Tyrosine Kinases
Luteolin
Protein-Tyrosine Kinases
Tyrosine
rac1 GTP-Binding Protein
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