Differential functional genomic effects of anti-inflammatory
phytocompounds on immune signaling in cancer cells
Shao-Chih Chiu1,2
1
Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
2
Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan.
Comparative subgenomic analysis of the immunological effects of different phytocompounds is considered as a useful approach to rapidly distinguish the complex and specific effects of a spectrum of candidate phytomedicines with potential clinical applications. Here we characterize the immunomodulatory activities of three anti-inflammatory phytocompounds (emodin, shikonin, and cytopiloyne) and a defined plant extract from Echinacea purpurea (BF/S+L/Ep) by focused DNA microarray analysis of selected immune-related genes, using LPS-stimulated THP-1 monocytic leukemia cells as a model. Shikonin and emodin significantly inhibited the early expression (within 0.5 h) of
approximately 50 genes, notably cytokines TNF-α, IL-1β and IL-4, chemokines CCL4 and
CCL8, and inflammatory modulators NFATC3 and PTGS2. In contrast, neither cytopiloyne nor BF/S+L/Ep inhibited the early expression of these 50 genes, but rather inhibited most late-stage expression (~12 h) of another immune gene subset. TRANSPATH database key node analysis identified the extracellular signal-regulated kinase (ERK) 1/2 activation pathway as the putative target of BF/S+L/Ep and cytopiloyne. Western blot confirmed that delayed inactivation of the ERK pathway was indeed demonstrable for these two preparations during the mid-stage (1 to 4 h) of LPS stimulation. We further identified ubiquitin pathway regulators, E6-AP and Rad23A, as possible key regulators for emodin and shikonin, respectively. The current focused DNA microarray approach rapidly identified important subgenomic differences in the pattern of immune cell-related gene expression in response to specific anti-inflammatory phytocompounds. These molecular targets and deduced networks may be of use in future biochemical and immunological classification of candidate anti-inflammatory phytomedicines.
