Augmented anti-proliferative effect in combined use of human lymphotoxin with a nitrosourea derivative, ACNU, and the involvement of glutathione redox cycle.
The cytotoxic or cytostatic effect of the combined use of human lymphotoxin (LT) with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) on L cells or Meth A tumor cells was studied. Simultaneous addition of LT derived from a human lymphoid cell line with ACNU (200 or 500 micrograms/ml) significantly augmented the cytotoxic effect. Similar augmented inhibition was obtained when LT was added to ACNU-treated L cells. The pre-treatment of Meth A tumor cells with ACNU (25 or 50 micrograms/ml) augmented recombinant human LT-mediated cytostasis. However, the addition of glutathione (1.0 mg/ml) to ACNU-treated Meth A tumor cells significantly nullified the augmented anti-proliferative effect of LT (10 U/ml). These results suggest that augmentation of the anti-proliferative effect on tumor cells could be induced through the combined use of LT with ACNU by lowering the intracellular level of glutathione.
Mashiba
H
H
Division of Immunology, National Kyushu Cancer Center, Fukuoka, Japan.
Matsunaga
K
K
Kakutani
T
T
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology; D007739:L Cells; D008233:Lymphotoxin-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015376:Nimustine / Q000008:administration & dosage / Q000494:pharmacology*; D010084:Oxidation-Reduction; D014407:Tumor Cells, Cultured
D008233:Lymphotoxin-alpha; D015376:Nimustine; D005978:Glutathione