Effect of extracellular ATP on cisplatin-induced cytotoxicity in human ovarian carcinoma cells.
BACKGROUND
Cisplatin resistance has been mainly associated with decreased cellular accumulation and increased intracellular glutathione (GSH) levels. ATP is known to increase the membrane permeability of cells and to decrease intracellular GSH levels. Our study aimed at using extracellular ATP to sensitize ovarian carcinoma cells towards cisplatin.


METHODS
The MTT assay was used to determine the EC(50) of cisplatin in the human ovarian carcinoma cell line A2780 and its cisplatin-resistant variant A2780cis. Intracellular platinum concentrations were determined using flameless atomic absorption spectrometry.


RESULTS
Preincubation and concomitant incubation with ATP did not alter the EC(50) of cisplatin. The presence of 100 muM ATP along with cisplatin decreased cell survival in A2780 but not in A2780cis cells. Extracellular ATP did not increase the cellular accumulation of cisplatin in both A2780 and A2780cis cells.


CONCLUSIONS
The presence of extracellular ATP during treatment with cisplatin leads to additive cytotoxicity in the sensitive A2780 but not in cisplatin-resistant A2780cis cells.
Rotte
Anand
A
Department of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, Bonn, Germany.
Garmann
Dirk
D
Buss
Irina
I
Jaehde
Ulrich
U
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D002945:Cisplatin / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D018625:Microscopy, Atomic Force; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000251:Adenosine Triphosphatases; D002945:Cisplatin