Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin

Innate Immun. 2014 Apr;20(3):301-11. doi: 10.1177/1753425913491789. Epub 2013 Jun 26.


Ganoderma lucidum (G. lucidum) is a medicinal mushroom long used in Asia as a folk remedy to promote health and longevity. Recent studies indicate that G. lucidum activates NK cells, but the molecular mechanism underlying this effect has not been studied so far. To address this question, we prepared a water extract of G. lucidum and examined its effect on NK cells. We observed that G. lucidum treatment increases NK cell cytotoxicity by stimulating secretion of perforin and granulysin. The mechanism of activation involves an increased expression of NKG2D and natural cytotoxicity receptors (NCRs), as well as increased phosphorylation of intracellular MAPKs. Our results indicate that G. lucidum induces NK cell cytotoxicity against various cancer cell lines by activating NKG2D/NCR receptors and MAPK signaling pathways, which together culminate in exocytosis of perforin and granulysin. These observations provide a cellular and molecular mechanism to account for the reported anticancer effects of G. lucidum extracts in humans.

Keywords: Ganoderma lucidum; NCR; NK cell; NKG2D; granulysin; perforin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antigens, Differentiation, T-Lymphocyte / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / physiology
  • Cytotoxicity, Immunologic / immunology*
  • Humans
  • Killer Cells, Natural / immunology*
  • Mice
  • Mitogen-Activated Protein Kinases / physiology
  • NK Cell Lectin-Like Receptor Subfamily K / biosynthesis*
  • Perforin / metabolism*
  • RNA / biosynthesis
  • RNA / isolation & purification
  • RNA, Small Interfering / pharmacology
  • Receptors, Cell Surface / biosynthesis
  • Reishi / chemistry*
  • Signal Transduction / physiology
  • Transfection


  • Antibodies
  • Antigens, Differentiation, T-Lymphocyte
  • GNLY protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • Perforin
  • RNA
  • Mitogen-Activated Protein Kinases