Clarithromycin suppresses invasiveness of human lung adenocarcinoma cells

Chemotherapy. 2007;53(2):77-84. doi: 10.1159/000098426. Epub 2007 Jan 5.

Abstract

Background: It has been speculated that clarithromycin (CAM), a 14-membered ring macrolide, possesses antitumor effects besides antimicrobial and anti-inflammatory effects.

Method: We evaluated the effects of CAM on the growth and invasiveness of A549 lung adenocarcinoma cells.

Results: Although CAM did not affect the growth of A549 cells, the Matrigel invasion assay showed that the potential of invasion was diminished by CAM treatment. When analyzed by flow cytometry, CAM suppressed alpha(2)- and beta(1)-integrin expression. Furthermore, thymidine phosphorylase (TP) expression was diminished by CAM treatment in a dose-dependent manner. A specific TP inhibitor also suppressed beta(1)-integrin expression in flow cytometric analysis.

Conclusions: These results suggest that CAM may suppress invasive activity of A549 cells in part by diminishing the expression of TP, alpha(2)- and beta(1)-integrin, which may be a downstream signal of the TP pathway, and that CAM could be useful in the treatment of lung adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Clarithromycin / pharmacology*
  • Humans
  • Integrin alpha2 / metabolism
  • Integrin beta1 / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mice
  • NIH 3T3 Cells
  • Neoplasm Invasiveness
  • Thymidine Phosphorylase / metabolism

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Integrin alpha2
  • Integrin beta1
  • Thymidine Phosphorylase
  • Clarithromycin