Systems Analysis Reveals Apoptosis and Macrophage Differentiation Induced by Ganoderma lucidum Polysaccharides

• Main Authors: Jia-Wei Hsu, 許家維
• Other Authors: Hsueh-Fen Juan
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/39788619976646092704

碩士 === 國立臺灣大學 === 分子與細胞生物學研究所 === 96 === Ganoderma lucidum has long been used to modulate the immune system in preventing or treating various human diseases in Asian countries. The biologically active compounds originally isolated and purified from Ganoderma lucidum were identified as polysaccharides, and the main fraction was designated as F3. In our study, F3 can activate many cytokines such as TNF-a in human leukemia cell line THP-1. Here, we integrated time-course microarray analysis and network modeling to study the F3-induced effects on THP-1 cells. In the microarray data analysis, we identified the differentially disturbed pathways with statistical significance based on Fisher’s exact test and false discovery rate. The pathway of apoptosis induction through death receptors is shown to be very significant in F3-treated THP-1 cells. Apoptosis-related assays were performed to show the apoptotic changes in F3-treated THP-1 cells. Caspase-3, 7, 8, 9 were cleaved into their active forms after F3 treatment. In addition, dynamic gene expression profiles showed that treatment of THP-1 cells with F3 might be capable of inducing cell differentiation. F3-treated THP-1 cells have capacity of enhancing macrophage differentiation, demonstrated by changes of cell adherence, cell cycle arrest, nitroblue tetrazolium reduction, and expression of differentiation markers including CD11b, CD14, CD68, matrix metalloproteinase-9, and myeloperoxidase. Furthermore, caspase cleavage and p53 activation were found to be significant in F3-induced THP-1 cells. General caspase inhibitor and p53 inhibitor reduced the percentage of F3-treated THP-1 cells to express CD11b and CD14. Altogether, these data indicated that F3 is able to induce cell death via death receptor signaling and differentiation of THP-1 cells into macrophages by activating caspase cascade and p53. Our results provide a molecular explanation for the properties of F3 on human leukemia cells by systems biology approach and put forth a valuable prospect for leukemia and cancer therapy.