Millettocalyxin B Inhibits Migratory Behavior of Lung Cancer Cells via Integrin α5 Suppression

Anticancer Res. 2021 Aug;41(8):3843-3849. doi: 10.21873/anticanres.15177.

Abstract

Background/aim: Integrin-targeting compounds have shown clinically significant benefits in many patients. Here, we examined the activity of millettocalyxin B, extracted from the stem bark of Millettia erythrocalyx, in lung cancer cells.

Materials and methods: The viability of human lung cancer cells was investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl tetrazoliumbromide (MTT) assay. Migration and invasion assays were performed. Phalloidin-rhodamine staining was used to determine the formation of filopodia. Western blot analysis and immunofluorescence staining were used to identify the signaling proteins involved in migration regulation.

Results: Non-toxic concentrations (0-25 μM) of millettocalyxin B reduced migration and invasion of lung cancer A549 cells. Filopodia were significantly reduced in millettocalyxin B-treated cells. The migration regulatory proteins including integrin α5, active FAK, active Akt, and Cdc42 were significantly decreased in Millettocalyxin B-treated cells.

Conclusion: Our findings revealed a novel anti-migration and anti-invasion effects and the underlying mechanism of millettocalyxin B, which may be exploited for cancer treatment.

Keywords: Akt; Cdc42; FAK; Millettocalyxin B; integrin; lung cancer; metastasis.

MeSH terms

  • A549 Cells
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Flavonoids / pharmacology*
  • Focal Adhesion Kinase 1 / metabolism
  • Humans
  • Integrin alpha5 / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pseudopodia / drug effects
  • cdc42 GTP-Binding Protein / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Flavonoids
  • Integrin alpha5
  • millettocalyxin B
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Proto-Oncogene Proteins c-akt
  • CDC42 protein, human
  • cdc42 GTP-Binding Protein