Augmentation of cytostatic effect of recombinant human lymphotoxin and involvement of glutathione redox cycle.

The effect of buthionine sulfoximine (BSO), an inhibitor of glutathione biosynthesis, in combined use with a nitrosourea derivative, ACNU, on the cytostatic effect of recombinant human lymphotoxin (rhLT) was studied in vitro. The simultaneous addition of 0.02 mM or 0.5 mM BSO and rhLT slightly augmented the inhibition of Meth A tumor cell proliferation. Similar tendency was observed when the target cells were treated with 0.02 mM or 0.5 mM BSO for 24 hr prior to the addition of rhLT. A marked augmentation of the antiproliferative effect was obtained when the target cells were treated in vitro with 0.005 mM or 0.02 mM BSO prior to the addition of 0.02 mM or 0.1 mM BSO and rhLT. The addition of ACNU simultaneously with rhLT to BSO-treated cells also augmented the antiproliferative effect. These results suggest that the glutathione redox cycle is closely related to the mechanism of LT-induced cytotoxicity.