Limitation of Nuclear Division by Protease Inhibitors in Cytochalasin-B-Treated Tumor Cells2

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Abstract
Treatment of tumorigenic mouse 3T12 and tumor-derived human RD cells with cytochalasin-B (CB) for 7 days resulted in highly multinucleate cells; e.g., >10% of 3T12 and >50% of RDcells contained ≥ 7 nuclei. When CB-treated cultures were examined cytogenetically, premature chromosome condensation (PCC) or pulverization was often seen. PCC was observed in 10% of CBtreated 3T12 cells and >20% of CB-treated RD cells. As described previously, CB treatment of normal cells resulted in binucleation, but cells with >2 nuclei were rare. After treatment with CB in the presence of protease inhibitor tosyl Iysl chloro methylketone (TLCK) or soybean trypsin inhibitor (SBTI), the frequency of 3T12 cells with >2 nuclei was greatly reduced and 3T12 cells with ≥7 nuclei were absent. PCC was also greatly reduced, occurring in 2 nuclei and the appearance of cells with ≥7 nuclei was eliminated. The frequency of PCC was lowered to <5%. Even when used at unusually high concentrations, SBTI had little effect on multinucleation and PCC in CB-treated RD cells. It is suggested that uncontrolled or unlimited nuclear division in neoplastic cells somehow depends on protease activity. The precise relationship between cellular protease activity and nuclear division remains to be elucidated.

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