Temporal effects of the novel antitumour pyridyl cyanoguanidine (CHS 828) on human lymphoma cells

CHS 828, a novel pyridyl cyanoguanidine, has shown potent antitumour activi ty both in vitro and in vivo and is currently undergoing phase I evaluation in humans in collaboration with the European Organization for Research and Treatment of Cancer (EORTC). Here we study the temporal effects of CHS 828 on cytotoxicity, protein and DNA synthesis, cellular morphology and ultra structure using the lymphoma cell line U-937 GTB as the primary tumour mode l. In vitro analysis of tumour cell survival in response to CHS 828 reveale d a cytotoxic effect progressively increased as a function of exposure time with maximum efficacy observed after 72 h. Activity of CHS 828 on U-937 GT B cells grown in vivo was also found. CHS 828 induced-cell death was depend ent on intact protein synthesis and most cells appeared to lose their membr ane integrity in the presence of a relatively well preserved nuclear struct ure. The results indicate that CHS 828 induced active and delayed cell deat h with a non-apoptotic morphology. (C) 2001 Elsevier Science Ltd. All right s reserved.