Polyamines are necessary for the survival of human small-cell lung carcinoma in culture.

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. alpha-Difluoromethylornithine, a specific enzyme-activated, 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 support the hypothesis that ornithine decarboxylase and the polyamines 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 alpha-difluoromethylornithine, a virtually nontoxic compound, may be potentially useful in the therapy of this human tumor.