Growth inhibition of lung cancer cells by adenosine 5′-triphosphate

Preliminary clinical data suggest that adenosine 5'-triphosphate (ATP) may inhibit lung tumor growth. Because studies of ATP on lung cancer cells are lacking, the aim of the present study was to explore effects of extracellular ATP on the growth and morphology of human lung tumor cells. Five human lung tumor cell lines derived from tumors with different cellular characteristics, i.e., a small cell carcinoma (GLC4), a large cell carcinoma (H460), a squamous cell carcinoma (H520), a mesothelioma (MERO82), and a papillary adenocarcinoma (H441), were exposed to 0, 0.5, 1, 2, and 3 mM ATP. Total cell numbers and dead or damaged cells were measured on days 1, 2, and 3. ATP induced a significant, dose-dependent growth inhibition in GLC4, H460, H520, and MERO82 cells. In contrast, H441 cells showed already maximal inhibition at 0.5 mM. Compared to untreated control cell lines, a significant growth inhibition (mean +/- SEM) of 65 +/- 5% (GLC4), 59 +/- 5% (H460), 45 +/- 5% (H520), 38 +/- 2% (MERO82), and 55 +/- 8% (H441) was shown after 3 days incubation with 3 mM ATP. ATP also induced changes in morphology and attachment to the substratum. Although not demonstrated by the Trypan Blue exclusion test, on photographs it seems that ATP induces death of GLC4 and H460 cells at higher concentrations. In conclusion, in four out of five explored lung tumor cell lines, ATP induces a dose-dependent growth inhibition. lung adenocarcinoma cells show already maximal inhibition at the lowest tested ATP dose. There is a relationship between growth inhibition and morphology changes. (C) 2003 Wiley-Liss, Inc.