trans-3-Methoxy-5-hydroxystilbene (MHS) from the rhizome of Alpinia nantonensis inhibits metastasis in human lung cancer cells

Phytomedicine. 2018 Nov 15;50:223-230. doi: 10.1016/j.phymed.2018.04.010. Epub 2018 Apr 5.

Abstract

Background: Alpinia nantoensis (Zingiberaceae) is an aromatic plant endemic to Taiwan, which is used as food flavoring and traditional herbal medicine. The biological activities of compounds isolated from this plant are rarely investigated.

Purpose: The present study was aimed to investigate the anti-metastatic potential of trans-3‑methoxy‑5-hydroxystilbene (MHS) a major stilbene isolated from the rhizomes of A. nantonensis.

Methods: We investigated the anti-metastatic potential of MHS on human non-small cell lung carcinoma (A549) cell line using wound healing, trans-well, western blot, zymography and immunofluorescence assays.

Results: Initial cytotoxicity assay showed that treatment with MHS did not exhibit cytotoxicity to A549 cells up to the concentration of 40 µM. Further in vitro wound healing and transwell chamber assays revealed that MHS significantly inhibited tumor cell migration in a dose-dependent manner, which is associated with inhibition of matrix mettalloprotinase-2 (MMP-2) and matrix mettalloprotinase-9 (MMP-9) at both enzyme and protein levels. The inhibition of MMPs activity by MHS was reasoned by suppression of their corresponding transcription factor, β-catenin as indicated by reduced levels of β-catenin in the nucleus. MHS also regulates epithelial-to-mesenchymal transition (EMT) by increasing E-cadherin and occludin as well as decreasing N-cadherin levels in A549 cells. Furthermore, pre-treatment with MHS significantly inhibited A549 cells migration and EMT in TGF-β induced A549 cells.

Conclusion: To the best of our knowledge, this is the first report demonstrating that MHS, a plant-derived stilbene has a promising ability to inhibit lung cancer cell metastasis in vitro.

Keywords: Alpinia nantoensis; Epithelial-to-mesenchymal transition; Lung cancer; Metastasis; Trans-3‑methoxy‑5-hydroxystilbene.

MeSH terms

  • A549 Cells
  • Alpinia / chemistry*
  • Antigens, CD / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cadherins / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Lung Neoplasms / pathology
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Metastasis
  • Rhizome / chemistry
  • Stilbenes / pharmacology*
  • Taiwan
  • Transforming Growth Factor beta
  • beta Catenin / metabolism

Substances

  • Antigens, CD
  • Antineoplastic Agents, Phytogenic
  • CDH1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Stilbenes
  • Transforming Growth Factor beta
  • beta Catenin
  • MMP9 protein, human
  • Matrix Metalloproteinase 9