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

Int J Cancer. 1997 Mar 17;70(6):699-705. doi: 10.1002/(sici)1097-0215(19970317)70:6<699::aid-ijc12>;2-5.


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)-1 beta, tumor necrosis factor (TNF)- alpha, and IL-6 in macrophage cultures treated with PS-G (100 micrograms/ml) were 5.1-, 9.8- and 29-fold higher, respectively, than those of untreated controls. In addition, the release of interferon (IFN)- gamma from T lymphocytes was also greatly promoted in the presence of PS-G (25-100 micrograms/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 micrograms/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- alpha and IFN- gamma, and these 2 cytokines acted synergistically on the inhibition of leukemic-cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Basidiomycota / chemistry*
  • Cytokines / biosynthesis*
  • Cytotoxicity, Immunologic
  • Drug Screening Assays, Antitumor
  • Drugs, Chinese Herbal / pharmacology*
  • Humans
  • Interleukin-1 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Leukemia / drug therapy
  • Leukemia / pathology
  • Lipopolysaccharide Receptors
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology*
  • Macrophages / drug effects
  • Polysaccharides / pharmacology*
  • Reishi
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Adjuvants, Immunologic
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antineoplastic Agents
  • CD68 antigen, human
  • Cytokines
  • Drugs, Chinese Herbal
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • Polysaccharides
  • Tumor Necrosis Factor-alpha