Abstract
Ganoderma lucidum is one of most widely used herbal medicine and functional food in Asia, and ganoderic acids (GAs) are its active ingredients. Regulation of GA biosynthesis and enhancing GA production are critical to using G. lucidum as a medicine. However, regulation of GA biosynthesis by various signaling remains poorly understood. This study investigated the role of apoptosis signaling on GA biosynthesis and presented a novel approach, namely apoptosis induction, to increasing GA production. Aspirin was able to induce cell apoptosis in G. lucidum, which was identified by terminal deoxynucleotidyl transferase mediated dUPT nick end labeling assay positive staining and a condensed nuclear morphology. The maximum induction of lanosta-7,9(11), 24-trien-3α-01-26-oic acid (ganoderic acid 24, GA24) production and total GA production by aspirin were 2.7-fold and 2.8-fold, respectively, after 1 day. Significantly lower levels of GA 24 and total GAs were obtained after regular fungal culture for 1.5 months. ROS accumulation and phosphorylation of Hog-1 kinase, a putative homolog of MAPK p38 in mammals, occurred after aspirin treatment indicating that both factors may be involved in GA biosynthetic regulation. However, aspirin also reduced expression of the squalene synthase and lanosterol synthase coding genes, suggesting that these genes are not critical for GA induction. To the best of our knowledge, this is the first report showing that GA biosynthesis is linked to fungal apoptosis and provides a new approach to enhancing secondary metabolite production in fungi.
Highlights
Ganoderma lucidum is a basidiomycete fungus and has been one of mostly widely used folk remedy in Asia for thousands years
Effect of aspirin on the production of ganoderic acids and fungal biomass To evaluate the effect of aspirin on ganoderic acid production, BCRC 36111 was cultured on potato dextrose agar (PDA) for 4 days and incubated with 0.5–8 mM aspirin for 1 day
Our recent findings have revealed that reactive oxygen species (ROS) and UV-B radiation are able to induce ganoderic acids (GAs) production and Hog-1 phosphorylation in G. lucidum [19]. These results suggest that Hog-1 may be associated with GA biosynthesis, which is known to be triggered by various environmental cues in G. lucidum
Summary
Ganoderma lucidum is a basidiomycete fungus and has been one of mostly widely used folk remedy in Asia for thousands years. Patients with diseases such as cancer, chronic hepatitis, inflammation, hypertension, and heart disease are treated with G. lucidum [1]. Ganoderic acids (GAs) are one of major compounds with pharmacological activity found in G. lucidum and these compounds belong to the triterpenoids. Ganoderic acids from G. lucidum have been shown to have numerous biological activities including anticancer activity, antiviral activity, hepatoprotective effects, anti-platelet aggregation effects, anti-oxidant activity, hypocholesterolemic activity, and the inhibition of histamine release [1,3]. Ganoderic acid T has been demonstrated to inhibit tumor metastasis by suppression of NF-kB activation [4]. Several studies indicated that mitochondria and p53 may be targeted by ganoderic acid T and Me to induce cell apoptosis [6,7,8]
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