Document Detail


Clarithromycin delays progression of bronchial epithelial cells from G1 phase to S phase and delays cell growth via extracellular signal-regulated protein kinase suppression.
MedLine Citation:
PMID:  16641444     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The nonsteroidal anti-inflammatory drugs have been shown to support cytoprotection of cells by shifting cells toward a quiescent state (G(0)/G(1)). Extracellular signal-regulated kinase (ERK) is required for cells to pass from G(1) phase into S phase, and macrolide antibiotics can inhibit ERK1/2 phosphorylation. However, previous reports suggest that macrolide antibiotics do not affect cell growth in bronchial epithelial cells. Therefore, we studied normal human bronchial epithelial (NHBE) cells to determine whether clarithromycin (CAM) suppresses ERK, delays bronchial epithelial cells from progressing to S phase, and delays cell growth. Exposure to CAM at 10 microg/ml daily over 4 days irreversibly decreased the cell proliferation with and without growth supplements (P < 0.0001). CAM also inhibited ERK1/2 phosphorylation over the first 90 min of exposure (P < 0.05 for 30 min, P < 0.0001 for 60 min, and P < 0.01 for 90 min) and decreased the ratio of phosphorylated ERK1/2 (pERK1/2) to total ERK1/2 (tERK1/2) (P < 0.0001). Incubation with CAM for 48 h increased the proportion of cells in G(1) phase (means +/- standard deviations) from 63.5% +/- 0.9% to 79.1% +/- 1.4% (P < 0.0001), decreased that in S phase from 19.8% +/- 1.2% to 10.0% +/- 2.1% (P < 0.01), and decreased that in G(2)/M phase from 16.7% +/- 0.4% to 11.0% +/- 0.8% (P < 0.001). In contrast, the ratio of pMEK1/2 to tMEK1/2 was not altered after exposure to CAM. These results suggest that macrolide antibiotics can delay the progression of NHBE cells from G(1) phase to S phase and can slow cell growth, probably through the suppression of ERK1/2.
Authors:
Masaharu Shinkai; Jun Tamaoki; Hideo Kobayashi; Soichiro Kanoh; Kazuo Motoyoshi; Tim Kute; Bruce K Rubin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  50     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-04-27     Completed Date:  2006-06-09     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1738-44     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1081, USA.
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MeSH Terms
Descriptor/Qualifier:
Anti-Bacterial Agents / administration & dosage,  pharmacology*
Bronchi / cytology,  enzymology,  metabolism*
Cell Line
Cell Proliferation / drug effects*
Cell Survival / drug effects
Clarithromycin / administration & dosage,  pharmacology*
DNA / analysis
Epithelial Cells / metabolism
Extracellular Signal-Regulated MAP Kinases / metabolism*
Flow Cytometry
G1 Phase / drug effects*
Humans
Models, Biological
S Phase / drug effects*
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 81103-11-9/Clarithromycin; 9007-49-2/DNA; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
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