The anti‐tumor effect of Ganoderma Lucidum is mediated by cytokines released from activated macrophages and T lymphocytes

The present study was to ascertain the immunomodulating and anti‐tumor effects of Ganoderma (G.) lucidum. Polysaccharides (PS) from fresh fruiting bodies of G. lucidum (PS‐G) were isolated and used to potentiate cytokine production by human monocytes‐macrophages and T lymphocytes. Our results had shown that the levels of interleukin (IL)‐Iβ, tumor necrosis factor (TNF)‐α, and IL‐6 in macrophage cultures treated with PS‐G (100 μg/ml) were 5.1‐, 9.8‐ and 29‐fold higher, respectively, than those of untreated controls. In addition, the release of interferon (IFN)‐γ from T lymphocytes was also greatly promoted in the presence of PS‐G (25–100 μ/ml). Furthermore, these cytokine‐containing mononuclear cell‐conditioned media (PSG‐MNC‐CM) were found to suppress the proliferation and clonogenicity of both the HL‐60 and the U937 leukemic cell lines. DNA labeling and gel electrophoresis showed that treatment with PSG‐MNC‐CM markedly induced leukemic‐cell apoptosis. Flow‐cytometric analysis revealed that few (2.3 ± 0.8%) apoptotic cells were seen in the control cultures, while PSG‐MNC‐CM treatment resulted in a significant increase in the apoptotic population both in the HL‐60 (38.3 ± 4.5%) and in the U937 (44.5 ± 3.8%) cells. In addition, 40 to 45% of the treated leukemic cells were triggered to differentiate into mature monocytic cells expressing CD14 and CD68 surface antigens. However, PS‐G alone had no such effects even at a higher dose of 400 μg/ml. Since untreated macrophages and T lymphocytes produced little or no cytokine, and normal MNC‐CM did not suppress leukemic cell growth, it was suggestive that the anti‐tumor activity of PSG‐MNC‐CM was derived from the elevated levels of cytokines. Antibody‐neutralization studies further revealed that the anti‐tumor cytokines in the PSG‐MNC‐CM were mainly of TNF‐α and IFN‐γ, and these 2 cytokines acted synergistically on the inhibition of leukemic‐cell growth. Int. J. Cancer 70:699–705, 1997. © 1997 Wiley‐Liss, Inc.