EFFECTS OF COUMARIN (1,2-BENZOPYRONE) ON LYMPHOCYTE, NATURAL-KILLER CELL, AND MONOCYTE FUNCTIONS INVITRO

Abstract

We have demonstrated in a pilot study that the combination of coumarin (1,2-benzopyrone) and cimetidine is capable of producing objective antitumor responses in patients with advanced cell carcinoma. In a previous study, we used monoclonal antibody labeling techniques to monitor peripheral blood lymphocytes and monocytes in patients with advanced malignancies treated with coumarin and cimetidine. While there was no quantitative alteration in T-lymphocytes, B-lymphocytes, natural killer (NK) cells, or cells bearing Ia antigen there was an increase in the percentage of CD-14 (M5E2+) monocytes and DR+ monocytes by 2 weeks on therapy that persisted over the 8 weeks of monitoring. Because patients received coumarin for 2 weeks prior to institution of cimetidine, these changes were attributed to coumarin. In this report, we present the results of in viro studies designed to determine if coumarin alters the functional properties of normal peripheral blood lymphocytes, NK cells, or monocytes. In a standard NK cytolytic assay, coumarin failed to produce any significant alteration in NK activity against K562, ACHN, or Caki-2 cell lines. Coumarin did produce an augmentation of lymphocytes mitogenic response to phytohemagglutinin but not to concanavalin A or pokeweed mitogen. Coumarin produced a modest suppression of superoxide anion and hydrogen peroxide generation by monocytes but not by macrophages. The effect of coumarin on antigen processing of tetanus toxoid by macrophages was examined using normal donor cells. While an augmentation of antigen processing was noted in some normal donors, this was an inconsistent and inconclusive finding. Further studies are required to define the precise effects of coumarin on immune cell populations from both normal subjects and cancer patients.