TUBOCURARIN INDUCES THE WIDE SPECTRUM OF CYTOLYTIC EFFECTS IN TUMOR-CELLS

Tubocurarin was shown to mediate a wide spectrum of cytolytic processes in tumor cells while peritoneal murine macrophages were resistant to its action. Group I of these processes was due to rapid (within 1-3 h) and nonspecific lysis mediated by relatively high (> 10(-5) M) concentrations of tubocurarin. Membrane damage with subsequent osmotic lysis was associated with these events. Processes of groups II and III were highly specific, cytolysis of group II having developed within 4-5 h and characterized by saturation at 5 X 10(-7) M. It was proposed that two types of necrosis contributed to the processes of group II. These pathways were induced by different concentrations of tubocurarin and also differed in their sensitivity to lysosomal inhibitor NH4Cl. Cytolysis of group III was associated with apoptosis and developed within 8-24 h. The significant acceleration of DNA fragmentation and subsequent cell death was achieved by increase of tubocurarin concentration from 5 X 10(-8) to 10(-6) M.