The roles of mitotic arrest and protein synthesis in induction of apoptosis and differentiation in neuroblastoma cells in culture

Studies of the response of neural crest tumor cells to the DNA cleaving antimitotic agent, neocarzinostatin, have left unanswered the question of whether the DNA cleavage per se or the antimitotic effect is responsible for this response. Furthermore, they do not define the timeframe within which a cell commits to its fate. Using the reversible microtubule-active agent, vinblastine, we now demonstrate that mitotic arrest, even without DNA cleavage, results in the same cellular changes as those seen with neocarzinostatin treatment. The commitment of the cell to its fate occurs within a 15 min treatment with vinblastine, and requires new protein synthesis. The immediate early gene products, c-Fos and c-Jun, appear not to be determinants of this process.