Cytokines secreted by lymphokine-activated killer cells induce endogenous nitric oxide synthesis and apoptosis in DLD-1 colon cancer cells.
Cell Immunol
; 203(2): 84-94, 2000 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-11006006
ABSTRACT
IL-2-activated killer lymphocytes (LAK cells) secrete inflammatory cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNFalpha) that can induce nitric oxide (NO) synthesis. We evaluated whether LAK cells could activate NO synthesis in human cancer cells. LAK cells and their culture supernatants induced NO synthesis in DLD-1 colon cancer cells in a dose-dependent manner. NO synthesis was inhibited completely by blocking antibodies to IFN-gamma, demonstrating a key role for this LAK cell cytokine in regulating NO synthesis. The addition of TNFalpha antibodies resulted in partial inhibition. Induction of iNOS mRNA and protein expression in DLD-1 cells was detected. Endogenous NO production inhibited DLD-1 cell proliferation and induced apoptosis, processes that were inhibitable by the NO synthase inhibitor N(G)-monomethyl-l-arginine. Our study has identified a novel, non-contact-dependent LAK cell cytotoxic mechanism induction of growth inhibition and programmed cell death due to endogenous NO synthesis in susceptible human cancer cells.
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Base de datos:
MEDLINE
Asunto principal:
Células Asesinas Activadas por Linfocinas
/
Interferón gamma
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Factor de Necrosis Tumoral alfa
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Apoptosis
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Óxido Nítrico
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cell Immunol
Año:
2000
Tipo del documento:
Article