N-acetyl-L-cysteine Exhibits Antitumoral Activity by Increasing Tumor Necrosis Factor 
-Dependent T-Cell Cytotoxicity
Yves Delneste,
Pascale Jeannin,
Laurent Potier,
Pedro Romero, and
Jean-Yves Bonnefoy
From the Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development SA, Immunology Department, Geneva, Switzerland; and the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
Because of its anticarcinogenic and antimutagenic properties, N-acetyl-L-cysteine (NAC) has been proposed for cancer treatment. Here we present a mechanism of action for NAC in cancer. Our data show that NAC (1) induces an early and sustained increase of membrane tumor necrosis factor 
(TNF) expression on human stimulated-peripheral blood (PB) T cells and (2) increases membrane TNF-RI and TNF-RII on tumoral cell lines and on T cells after stimulation. These effects result from an early inhibition of both TNF and TNF-R shedding, as well as a later increase of the respective mRNA expression. Consequently, NAC confers cytotoxic properties to human PB T cells through a membrane TNF-dependent pathway. In vivo, NAC given orally inhibits tumor appearance in more than a third (18 out of 50) B6D2F1 mice injected with L1210 lymphoma cells. Spleen cells from protected mice killed L1210 lymphoma cells in vitro in a membrane TNF-dependent manner. Furthemore these mice were resistant to a second inoculation of L1210 cells without further treatment with NAC. Thus, NAC exhibits a potent antitumoral activity by modulating TNF and TNF-R processing without showing any in vitro and in vivo toxicity.
Blood, Vol. 90 No. 3 (August 1), 1997:
pp. 1124-1132
© 1997 by The American Society of Hematology.
