Document Detail

Steroids affect collateral sensitivity to gemcitabine of multidrug-resistant human lung cancer cells.
MedLine Citation:
PMID:  11282108     Owner:  NLM     Status:  MEDLINE    
Gemcitabine is phosphorylated by deoxycytidine kinase and thymidine kinase 2 and during S-phase incorporated into DNA. The steroids cortisol and dexamethasone, which regulate cell proliferation and gene expression, are pumped out of the cell by the membrane efflux pumps P-glycoprotein and multidrug resistance-associated protein (MRP), which are blocked by verapamil. In parental non-small cell lung cancer (NSCLC) cells (SW1573), 5 microM cortisol and 100 nM dexamethasone decreased sensitivity to gemcitabine. However, both cortisol and dexamethasone only decreased sensitivity with verapamil in MRP (2R120) and P-glycoprotein (2R160) overexpressing variants. Cortisol decreased deoxycytidine kinase activity in SW1573 cells and cortisol with verapamil in 2R120 and 2R160 cells. Dexamethasone with verapamil decreased deoxycytidine kinase activity in 2R160. Cortisol decreased thymidine kinase 2 activity in 2R120 and 2R160 cells. Dexamethasone decreased thymidine kinase 2 activity in SW1573, 2R120 and 2R160 cells. In conclusion, since dexamethasone is frequently used to treat side effects of oncolytic therapy, a decrease of sensitivity to gemcitabine by steroids might be clinically relevant.
A M Bergman; H M Pinedo; G J Peters
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  416     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-04-03     Completed Date:  2001-07-26     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  19-24     Citation Subset:  IM    
Department of Oncology, VU Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, Netherlands.
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MeSH Terms
Cell Division / drug effects
Deoxycytidine / analogs & derivatives,  pharmacology*
Deoxycytidine Kinase / drug effects,  metabolism
Dexamethasone / pharmacology*
Drug Interactions
Drug Resistance, Multiple
Hydrocortisone / pharmacology*
P-Glycoprotein / drug effects*,  metabolism
Tumor Cells, Cultured
Verapamil / pharmacology
Reg. No./Substance:
0/P-Glycoprotein; 50-02-2/Dexamethasone; 50-23-7/Hydrocortisone; 52-53-9/Verapamil; 951-77-9/Deoxycytidine; B76N6SBZ8R/gemcitabine; EC Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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