Polyamines are necessary for the survival of human small-cell lung carcinoma in culture (ornithine decarboxylase/inhibitor/a-difluoromethylornithine/spheroids)

Many human small-cell lung carcinoma culture lines grow as multicellular aggregate spheroids, for which high L- dopa decarboxylase activity is a marker. During the initial cell aggregation and the exponential growth phase, there is a marked increase in ornithine decarboxylase activity and an accumulation of polyamines. a-Difluoromethylornithine, a specific enzyme-ac- tivated, irreversible ornithine decarboxylase inhibitor, blocks the increase in ornithine decarboxylase activity and in polyamines and inhibits human small-cell lung carcinoma cell growth. After the onset of a decreased proliferation rate, the multicellular spheroid aggregates become poorly formed, cell loss ensues, and there is a decrease in L-dopa decarboxylase activity. These findings sup- port the hypothesis that ornithine decarboxylase and the poly- amines play an essential role not only in the proliferative phase but also in the viability of human small-cell lung carcinoma cells in culture. The results suggest that at-difluoromethylornithine, a virtually nontoxic compound, may be potentially useful in the ther- apy of this human tumor.