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


CONCLUSIONS
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.
Cheng
Kun-Chieh
KC
Department of Life Science, National Taiwan University, Taipei 106, Taiwan. jerekcheng@gmail.com
Huang
Hsuan-Cheng
HC
Chen
Jenn-Han
JH
Hsu
Jia-Wei
JW
Cheng
Hsu-Chieh
HC
Ou
Chern-Han
CH
Yang
Wen-Bin
WB
Chen
Shui-Tein
ST
Wong
Chi-Huey
CH
Juan
Hsueh-Fen
HF
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D053218:Receptors, Death Domain / Q000235:genetics / Q000378:metabolism; D020940:Reishi / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D016207:Cytokines; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011134:Polysaccharides; D053218:Receptors, Death Domain