Document Detail

Lack of correlation of MRP and gamma-glutamylcysteine synthetase overexpression with doxorubicin resistance due to increased apoptosis in SV40 large T-antigen-transformed human mesothelial cells.
MedLine Citation:
PMID:  9788569     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Evidence suggests that viral proteins such as simian virus large T-antigen (SV40 TAg) play a role in the response of cancer cells to chemotherapeutic agents. In this study, we investigated whether SV40 TAg-immortalized human mesothelial cells express drug resistance-related proteins and display resistance to chemotherapy, and whether SV40 TAg transformation affects apoptosis. METHODS: We determined the mRNA and protein levels of the multidrug resistance-associated protein (MRP), gamma-glutamylcysteine synthetase heavy subunit (gamma-GCSh), and P-glycoprotein (product of the MDR1 gene) by RT-PCR and Western blotting, respectively, in normal human mesothelial (NHM) cell and SV40 TAg-transformed human mesothelial (Met-5A) cells. The effect of increasing concentrations of doxorubicin (DOX) on these cells was investigated using an MTT cytotoxicity assay, and the glutathione (GSH) content was measured spectrophotometrically. DOX accumulation in these cells was measured by treating the cells with [14C]DOX followed by scintillation counting. Cytoplasmic bNA fragmentation due to apoptosis following DOX treatment of the cells was quantitated by ELISA. RESULTS: We showed that the MRP and gamma-GCSh genes, but not MDR1, are coordinately overexpressed in Met-5A cells compared with NHM cells. Expression of MRP protein as detected by an anti-MRP antibody correlated with increased GSH levels and decreased accumulation of [14C]DOX in Met-5A cells compared with NHM cells. However, Met-5A cells were twofold more sensitive to DOX than NHM cells. In addition, quantitative measurement of apoptosis when cells were treated with 0.05 and 0.5 microM DOX revealed that drug-induced apoptotic cell death was increased about 1.4- and 3.0-fold, respectively, in Met-5A cells compared with NHM cells. CONCLUSIONS: These results suggest that increased levels of apoptosis might help overcome the DOX resistance effects of MRP/gamma-GCSh overexpression in SV40 TAg-transformed Met-5A cells.
B Ogretmen; H Bahadori; M McCauley; A Boylan; M Green; A R Safa
Related Documents :
19291609 - 20s-protopanaxadiol inhibits p-glycoprotein in multidrug resistant cancer cells.
8566169 - Opiates inhibit ion conductances elicited by cell swelling and camp in cultured cells.
11642329 - Circumvention of acquired resistance to doxorubicin in k562 human leukemia cells by oxa...
2896069 - Pharmacological and biological evidence for differing mechanisms of doxorubicin resista...
8391919 - Localization of a novel multidrug resistance-associated gene in the ht1080/dr4 and h69a...
7909709 - Probenecid-resistant j774 cell expression of enhanced organic anion transport by a mech...
2510989 - Pituitaries transplanted under the renal capsule contain functional growth hormone (gh)...
24517569 - In vitro biocompatibility of a dentine substitute cement on human mg63 osteoblasts cell...
10992519 - Aggregation substance increases adherence and internalization, but not translocation, o...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  42     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  1998  
Date Detail:
Created Date:  1998-11-04     Completed Date:  1998-11-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  441-6     Citation Subset:  IM    
Department of Experimental Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston 29425, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
ATP-Binding Cassette Transporters / genetics*
Antigens, Polyomavirus Transforming
Base Sequence
Cell Line, Transformed
DNA Primers
Doxorubicin / pharmacology*
Drug Resistance, Multiple / genetics
Drug Resistance, Neoplasm / genetics
Epithelium / drug effects
Glutamate-Cysteine Ligase / genetics*
Glutathione / metabolism
Multidrug Resistance-Associated Proteins
RNA, Messenger / genetics
Simian virus 40 / immunology
Grant Support
Reg. No./Substance:
0/ATP-Binding Cassette Transporters; 0/Antigens, Polyomavirus Transforming; 0/DNA Primers; 0/Multidrug Resistance-Associated Proteins; 0/RNA, Messenger; 23214-92-8/Doxorubicin; 70-18-8/Glutathione; EC Ligase

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

Previous Document:  Pharmacokinetics of temozolomide in association with fotemustine in malignant melanoma and malignant...
Next Document:  Antihelicase action of CI-958, a new drug for prostate cancer.