Author/Authors :
Kwak، نويسنده , , Jae-Yong and Han، نويسنده , , Myung Kwan and Choi، نويسنده , , Kyoung-Seong and Park، نويسنده , , In-Hye and Park، نويسنده , , Sang-Youel and Sohn، نويسنده , , Myung-Hee Y. Kim، نويسنده , , Uh-Hyun and McGregor، نويسنده , , John R. and Samlowski، نويسنده , , Wolfram E. and Yim، نويسنده , , Chang-Yeol، نويسنده ,
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 NG-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.
