Cytokines secreted by lymphokine-activated killer cells induce endogenous nitric oxide synthesis and apoptosis in DLD-1 colon cancer cells

Jae Yong Kwak, Myung Kwan Han, Kyoung Seong Choi, In Hye Park, Sang Youel Park, Myung Hee Sohn, Uh Hyun Kim, John R. McGregor, Wolfram E. Samlowski, Chang Yeol Yim

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

IL-2-activated killer lymphocytes (LAK cells) secrete inflammatory cytokines such as interferon-γ (IFN-γ) and tumor necrosis factor α (TNFα) 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-γ, demonstrating a key role for this LAK cell cytokine in regulating NO synthesis. The addition of TNFα 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. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)84-94
Number of pages11
JournalCellular Immunology
Volume203
Issue number2
DOIs
StatePublished - 1 Aug 2000

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