Publications

Modulation of cell growth and cisplatin sensitivity by membrane gamma-glutamyltransferase in melanoma cells  (2006)

Authors:
FRANZINI M; CORTI A; LORENZINI E; PAOLICCHI A; POMPELLA A; DE CESARE M; PEREGO P; GATTI L; R. LEONE; APOSTOLI P; ZUNINO F
Title:
Modulation of cell growth and cisplatin sensitivity by membrane gamma-glutamyltransferase in melanoma cells
Year:
2006
Type of item:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Language:
Inglese
Format:
A Stampa
Referee:
Name of journal:
European Journal of Cancer
ISSN of journal:
0959-8049
N° Volume:
42
Page numbers:
2623-2630
Keyword:
Antineoplastic Agents/therapeutic use; Cell Line; Tumor; Cisplatin/therapeutic use; Drug Interactions; Drug Resistance; Neoplasm; Glutathione/metabolism; Humans; Melanoma*/drug therapy; Melanoma*/enzymology; Skin Neoplasms*/drug therapy; Skin Neoplasms*/enzymology; gamma-Glutamyltransferase/physiology
Short description of contents:
The plasma membrane enzyme gamma-glutamyltransferase (GGT) is regarded as critical for the maintenance of intracellular levels of glutathione (GSH). GGT expression has been implicated in drug resistance through elevation of intracellular GSH. The dependence of intracellular GSH on GGT expression was not conclusively ascertained. The present study was designed to investigate the role of GGT and of intracellular GSH levels in modulating proliferation and sensitivity to cisplatin of melanoma cells. GGT transfection resulted in increased growth, both in vitro and in tumour xenografts. In addition, GGT-transfected cells exhibited reduced sensitivity to cisplatin associated with lower DNA platination. A decrease in intracellular GSH levels, rather than an increase, was observed in GGT-transfected cells; moreover, in cysteine-deficient conditions, the expression of GGT did not provide transfected cells with the ability of utilising extracellular GSH. In conclusion, these results indicate that GGT activity confers a growth advantage unrelated with intracellular glutathione supply, and are consistent with the interpretation that cisplatin resistance is the consequence of modifications of cellular pharmacokinetics as a result of extracellular drug inactivation by thiol metabolites originated by GGT-mediated GSH cleavage.
Product ID:
34408
Handle IRIS:
11562/230846
Deposited On:
March 16, 2012
Last Modified:
June 22, 2018
Bibliographic citation:
FRANZINI M; CORTI A; LORENZINI E; PAOLICCHI A; POMPELLA A; DE CESARE M; PEREGO P; GATTI L; R. LEONE; APOSTOLI P; ZUNINO F, Modulation of cell growth and cisplatin sensitivity by membrane gamma-glutamyltransferase in melanoma cells «European Journal of Cancer» , vol. 422006pp. 2623-2630

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