Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells

Life Sci. 2006 Dec 23;80(3):205-11. doi: 10.1016/j.lfs.2006.09.001. Epub 2006 Sep 6.


Ganoderma lucidum is a well-known traditional Chinese medicinal herb containing many bioactive compounds. Ganoderic acid T (GA-T), which is a lanostane triterpenoid purified from methanol extract of G. lucidum mycelia, was found to exert cytotoxicity on various human carcinoma cell lines in a dose-dependent manner, while it was less toxic to normal human cell lines. Animal experiments in vivo also showed that GA-T suppressed the growth of human solid tumor in athymic mice. It markedly inhibited the proliferation of a highly metastatic lung cancer cell line (95-D) by apoptosis induction and cell cycle arrest at G(1) phase. Moreover, reduction of mitochondria membrane potential (Delta psi(m)) and release of cytochrome c were observed during the induced apoptosis. Our data further indicate that the expression of proteins p53 and Bax in 95-D cells was increased in a time-dependent manner, whereas the expression of Bcl-2 was not significantly changed; thus the ratio of Bcl-2/Bax was decreased. The results show that the apoptosis induction of GA-T was mediated by mitochondrial dysfunctions. Furthermore, stimulation of the activity of caspase-3 but not caspase-8 was observed during apoptosis. The experiments using inhibitors of caspases (Z-VAD-FMK, Z-DEVD-FMK and Z-IETD-FMK) confirmed that caspase-3 was involved in the apoptosis. All our findings demonstrate that GA-T induced apoptosis of metastatic lung tumor cells through intrinsic pathway related to mitochondrial dysfunction and p53 expression, and it may be a potentially useful chemotherapeutic agent.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Caspase Inhibitors
  • Cell Line, Tumor
  • Cytochromes c / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Heptanoic Acids / chemistry
  • Heptanoic Acids / pharmacology*
  • Heptanoic Acids / therapeutic use
  • Humans
  • Lanosterol / analogs & derivatives
  • Lanosterol / chemistry
  • Lanosterol / pharmacology*
  • Lanosterol / therapeutic use
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Protease Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Reishi / chemistry
  • Tumor Suppressor Protein p53 / biosynthesis


  • Caspase Inhibitors
  • Heptanoic Acids
  • Protease Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Lanosterol
  • Cytochromes c
  • Caspase 3
  • Caspase 8