CYTOTOXICITY INDUCED BY ERYTHRINA-VARIEGATA SERINE PROTEINASE-INHIBITORS IN TUMOR HEMATOPOIETIC STEM-CELL LINES

Based on the soluble MTT tetrazolium/formazan assay, we evaluated the cytotoxicity of Erythrina variegata proteinase inhibitors in some tumo r hematopoietic stem cell lines. Among the proteinase inhibitors, EBI, which belongs to the Bowman-Birk family of inhibitors, was cytotoxic in relatively differentiated cells such as Molt4 and Jurkat derived fr om acute T lymphoblastic leukemia (T-ALL) cells specifically, but ETIa and ECI, which are classified into Kunitz family inhibitors, did not, It was suggested that the differences in the cytotoxicity might be du e to the molecular size of the inhibitors. The succinylation of lysine residue(s) of EBI led to about 50% loss of the trypsin inhibitory act ivity as compared with the authentic EBI. When Molt4 cells mere incuba ted with this derivative, no significant cytotoxicity was observed. Th is suggests that the proteinase inhibitory activity might be involved in the cytotoxicity in human tumor cell lines.