Document Detail

Sensitisation of Ehrlich ascitic tumour cells to methotrexate by inhibiting glutaminase.
MedLine Citation:
PMID:  16101144     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Glutaminase activity is correlated with cancer proliferation and with growth rate in normal cells. Ehrlich ascites tumour cells (EATC) and their derivative 0.28AS-2 cells, which express antisense glutaminase mRNA, show differences in both morphology and tumorigenic capacity. MATERIALS AND METHODS: Cell viability was determined with the microtetrazolium cytotoxicity test assay. Immunofluorescence staining with annexin-V and propidium iodide was carried out to assess the number of apoptotic cells. RESULTS: 0.28AS-2 cells are less resistant to H2O2 than EATC, since half the concentration of H2O2 caused a similar effect on the cell population in 24 h. Methotrexate significantly inhibited the proliferation of both EATC and 0.28AS-2 cells at concentrations higher than 64 nM after 48 h of exposure. CONCLUSION: 0.28AS-2 cells are highly sensitised to methotrexate. These results provide insights into the possible role of glutaminase in cancer therapy by demonstrating that the expression of antisense mRNA for glutaminase decreases chemoresistance to some pro-apoptotic agents.
Francisco J Alonso; Juan A Segura; Jorge Lora; Carolina Lobo; Beatriz Fernández-Molina; Javier Márquez; José M Matés
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  25     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2005 Sep-Oct
Date Detail:
Created Date:  2005-08-16     Completed Date:  2005-10-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  3315-20     Citation Subset:  IM    
Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, 29071 Málaga, Spain.
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MeSH Terms
Antimetabolites, Antineoplastic / pharmacology*
Apoptosis / drug effects
Carcinoma, Ehrlich Tumor / drug therapy*,  enzymology*,  pathology
Cell Growth Processes / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Synergism
Glutaminase / antagonists & inhibitors*,  genetics
Hydrogen Peroxide / pharmacology*
Methotrexate / pharmacology*
RNA, Antisense / genetics
RNA, Messenger / genetics
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/RNA, Antisense; 0/RNA, Messenger; 59-05-2/Methotrexate; 7722-84-1/Hydrogen Peroxide; EC

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