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Open Access Highly Accessed Research article

Ganoderma lucidum polysaccharides in human monocytic leukemia cells: from gene expression to network construction

Kun-Chieh Cheng12, Hsuan-Cheng Huang3, Jenn-Han Chen4, Jia-Wei Hsu5, Hsu-Chieh Cheng1, Chern-Han Ou16, Wen-Bin Yang7, Shui-Tein Chen78, Chi-Huey Wong789 and Hsueh-Fen Juan110115*

Author Affiliations

1 Department of Life Science, National Taiwan University, Taipei 106, Taiwan

2 Institute of Biotechnology, National Taipei University of Technology, Taipei 106, Taiwan

3 Institute of Biomedical Informatics, National Yang-Ming University, Taipei 112, Taiwan

4 School of Dentistry, National Defense Medical center, National Defense University, Taipei 114, Taiwan

5 Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan

6 Department of Electronic Engineering, National Taiwan University, Taipei, Taiwan

7 Institute of Biological Chemistry and the Genomics Research Center, Academia Sinica, Taipei 115, Taiwan

8 Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan

9 Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA

10 Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 106, Taiwan

11 Center for Systems Biology and Bioinformatics, National Taiwan University, Taipei 106, Taiwan

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BMC Genomics 2007, 8:411  doi:10.1186/1471-2164-8-411

Published: 9 November 2007

Abstract

Background

Ganoderma lucidum has been widely used as a herbal medicine for promoting health and longevity in China and other Asian countries. Polysaccharide extracts from Ganoderma lucidum have been reported to exhibit immuno-modulating and anti-tumor activities. In previous studies, F3, the active component of the polysaccharide extract, was found to activate various cytokines such as IL-1, IL-6, IL-12, and TNF-α. This gave rise to our investigation on how F3 stimulates immuno-modulating or anti-tumor effects in human leukemia THP-1 cells.

Results

Here, we integrated time-course DNA microarray analysis, quantitative PCR assays, and bioinformatics methods to study the F3-induced effects in THP-1 cells. Significantly disturbed pathways induced by F3 were identified with statistical analysis on microarray data. The apoptosis induction through the DR3 and DR4/5 death receptors was found to be one of the most significant pathways and play a key role in THP-1 cells after F3 treatment. Based on time-course gene expression measurements of the identified pathway, we reconstructed a plausible regulatory network of the involved genes using reverse-engineering computational approach.

Conclusion

Our results showed that F3 may induce death receptor ligands to initiate signaling via receptor oligomerization, recruitment of specialized adaptor proteins and activation of caspase cascades.