Clarithromycin suppresses invasiveness of human lung adenocarcinoma cells.
BACKGROUND
It has been speculated that clarithromycin (CAM), a 14-membered ring macrolide, possesses antitumor effects besides antimicrobial and anti-inflammatory effects.


METHODS
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.
Wada
Toshihiro
T
Division of Cardiology, Pulmonology, and Nephrology, Department of Internal Medicine and Therapeutics, Yamagata University School of Medicine, Yamagata, Japan.
Sata
Makoto
M
Sato
Jun
J
Tokairin
Yoshikane
Y
Machiya
Jun-ichi
J
Hirama
Noriyuki
N
Arao
Tsuyoshi
T
Inoue
Sumito
S
Takabatake
Noriaki
N
Shibata
Yoko
Y
Kubota
Isao
I
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017291:Clarithromycin / Q000494:pharmacology*; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D013939:Thymidine Phosphorylase / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D039421:Integrin alpha2; D019012:Integrin beta1; D013939:Thymidine Phosphorylase; D017291:Clarithromycin