Genomic Study on Ganoderma lucidum and Development of Ganoderma Metabolites for Cancer Adjuvant Therapy

摘要

Ganoderma lucidum and the related fungal species have been used in Chinese medicine and as a health food for years. These fungi exhibit a very broad spectrum of biological activities and pharmacological functions. Recently, researchers from the Veterans General Hospital-Taipei, National Yang-Ming University, National Taiwan University, and National Health Research Institutes have formed a Ganoderma consortium and completed the whole-genome sequencing (～5X) of G. lucidum by using a shotgun method. Bioinformatic study, particularly on the genes and gene cluster that are responsible for the biosynthesis of immuno-modulatory polysaccharides in G. lucidum, is currently underway. We have also elucidated the potential of Ganoderma as an adjuvant therapy for human hepatocellular carcinoma. The aim is to differentiate between hepatocytes and hepatoma cells in response to apoptosis induction by inhibiting the multiple mevalonate-demanding pathways. Human hepatoma cells (HepG2 and Hep3B) were chosen as the cellular models. Lovastatin, a lipophilic and liver-specific HMG-CoA reductase inhibitor, was used to reduce cellular mevalonate pool. The sensitivity of HepG2 cells to lovastatininduced apoptosis was similar to that of the isolated hepatocytes. Hep3B cells were more sensitive to mevalonate-deprivation. The advantage of combination treatment by using lovastatin and Ganoderma to induce apoptosis in Hep3B cells was demonstrated. An oxygenated triterpene-rich fraction of Ganoderma effectively induced apoptosis in mevalonate-deprived hepatoma cells. Reduction of cellular mevalonate pool to a stage that cholesterol synthesis was suppressed and cell growth was arrested greatly enhanced the sensitivity of hepatoma cells to a second anticancer agent including Ganoderma. Animal study by using nude mice inoculated with human hepatoma cells (Hep3B/T2) demonstrated that combination treatment of lovastatin and Ganoderma was more effective to reduce tumor growth. Microarray technique also allowed us to look into the gene expression profiles affected by this medicinal fungus. The potential of Ganoderma as an agent for cancer adjuvant therapy will be discussed.