Ganoderic acid D
Ganoderic acid D treatment for 48h inhibits the proliferation of HeLa human cervical carcinoma cells with an IC(50) value of 17.3 +/- 0.3 microM.
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Mol Cell Proteomics. 2008 May;7(5):949-61.
Proteomics characterization of the cytotoxicity mechanism of ganoderic acid D and computer-automated estimation of the possible drug target network.[Pubmed:
18166740]
Triterpenes isolated from Ganoderma lucidum could inhibit the growth of numerous cancer cell lines and were thought to be the basis of the anticancer effects of G. lucidum. Ganoderic acid D (GAD) is one of the major components in Ganoderma triterpenes. GAD treatment for 48 h inhibited the proliferation of HeLa human cervical carcinoma cells with an IC(50) value of 17.3 +/- 0.3 microM. Flow cytometric analysis and DNA fragmentation analysis indicated that Ganoderic acid D induced G(2)/M cell cycle arrest and apoptosis.
METHODS AND RESULTS:
To identify the cellular targets of Ganoderic acid D, two-dimensional gel electrophoresis was performed, and proteins altered in expressional level after Ganoderic acid D exposure of cells were identified by MALDI-TOF MS/MS. The regulation of proteins was also confirmed by Western blotting. The cytotoxic effect of Ganoderic acid D was associated with regulated expression of 21 proteins. Furthermore these possible Ganoderic acid D target-related proteins were evaluated by an in silico drug target searching program, INVDOCK. The INVDOCK analysis results suggested that Ganoderic acid D could bind six isoforms of 14-3-3 protein family, annexin A5, and aminopeptidase B. The direct binding affinity of Ganoderic acid D toward 14-3-3 zeta was confirmed in vitro using surface plasmon resonance biosensor analysis. In addition, the intensive study of functional association among these 21 proteins revealed that 14 of them were closely related in the protein-protein interaction network.
They had been found to either interact with each other directly or associate with each other via only one intermediate protein from previous protein-protein interaction experimental results.
When the network was expanded to a further interaction outward, all 21 proteins could be included into one network.
CONCLUSIONS:
In this way, the possible network associated with Ganoderic acid D target-related proteins was constructed, and the possible contribution of these proteins to the cytotoxicity of Ganoderic acid D is discussed in this report.
Eur J Pharmacol . 2018 Apr 5;824:72-77.
Effect of ganoderic acid D on colon cancer Warburg effect: Role of SIRT3/cyclophilin D[Pubmed:
29374515]
Abstract
Ganoderic acid D (GAD) is a highly oxygenated tetracyclic triterpenoid. This study aims to assess the effects of GAD on the energy metabolism of colon cancer through the regulation of SIRT3 expression and whether this effect is related to acetylated cyclophilin D. The results demonstrated that GAD inhibits the energy reprogramming of colon cancer cells including glucose uptake, lactate production, pyruvate and acetyl-coenzyme production in colon cancer cells. Meanwhile, GAD upregulated the protein expression of SIRT3. Furthermore, the interruption of SIRT3 expression significantly reversed all the effects of SIRT3 on the energy reprogramming of colon cancer. In addition, GAD induced the deacetylated cyclophilin D (CypD) by SIRT3, whereas SIRT3-shRNA inhibited its combining effect on CypD. The energy reprogramming effects of GAD on colon cancer seem to be mediated by SIRT3 upregulation via acetylated CypD inhibition.
Keywords: Colon cancer; Cyclophilin D; Ganoderic acid D; Glucose metabolism; SIRT3; Warburg effect.
Drug Metab Dispos. 2012 Dec;40(12):2307-14.
Identification of metabolites of ganoderic acid D by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.[Pubmed:
22942320]
Ganoderic acid D (GD) is the major active triterpenoid in Ganoderma lucidum, a medicinal fungus used daily. However, the metabolic fate of Ganoderic acid D remains unknown. To know whether Ganoderic acid D is extensively metabolized, we first investigated the metabolism of Ganoderic acid D in vitro and in vivo.
METHODS AND RESULTS:
The metabolic profiles of the bile samples obtained from rats in vivo were almost the same as those obtained in vitro. Using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry, a total of 25 metabolites were identified from the bile sample. Few metabolites were found in the urine samples. These results indicated that biliary rather than renal clearance was the major route of excretion. The major metabolites were identified by comparison with the standard reference compounds. Metabolites at low concentrations were identified by interpreting the mass spectra. Both phase I and phase II metabolites were observed. The metabolic transformation included reduction, monohydroxylation, dihydroxylation, trihydroxylation, oxidation, desaturation, sulfation, and glucuronidation. The main metabolic soft spots in the chemical structure of Ganoderic acid D were the 3-carbonyl group, angular methyl groups, the 7-hydroxy group, and the 26-carboxylic acid moiety.
CONCLUSIONS:
Overall, this study gives us an insight into the metabolism of Ganoderic acid D, an active oxygenated tetracyclic triterpenoid.