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 tumor 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 from 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 due to the molecular size of the inhibitors. The succinylation of lysine residue(s) of EBI led to about 50% loss of the trypsin inhibitory activity as compared with the authentic EBI. When Molt4 cells were incubated with this derivative, no significant cytotoxicity was observed. This suggests that the proteinase inhibitory activity might be involved in the cytotoxicity in human tumor cell lines.
Ohba
H
H
Kyushu National Industrial Research Institute, Saga, Japan. ohba@kniri.go.jp
Nishikawa
M
M
Kimura
M
M
Yamasaki
N
N
Moriwaki
S
S
Itoh
K
K
D002470:Cell Survival / Q000187:drug effects; D004895:Erythrina / Q000737:chemistry*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D010946:Plants, Medicinal; D015842:Serine Proteinase Inhibitors / Q000633:toxicity*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015842:Serine Proteinase Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue