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α-Cyperone inhibitory effects on tumor-derived DNA trigger microglia by STING pathway
Peng Gao1, Ning Ding1, Jiaxin Lv1
1Department of Anesthesiology, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
Ethnopharmacological Relevance:
Cyperus rotundus L. (Cyperaceae) is a widespread herbal in China and widely used in Traditional Chinese Medicine for multiple effects such as anti-arthritic, anti-genotoxic, anti-mutagenic, anti-bacterial effects, and analgesic. α-Cyperone is an active compound in Cyperus rotundus and has analgesic effects, but the exact molecular mechanisms require further investigations.
Materials And Methods:
Tumor-derived DNA isolated from Lewis cell lines was transfected into microglia, and analyzed for stimulator of interferon genes (STING) effects. The downstream protein, such as interferon regulatory factor 3 (IRF3) and p65 nuclear factor-κB (NF-κB) were treated with STING siRNA and 5,6-dimethyllxanthenone-4-acetic acid (DMXAA) in microglia. The α-Cyperone effect on microglia was also investigated.
Results:
Tumor-derived DNA activate microglia by upregulation of STING and downstream proteins. STING siRNA was reduced to its downstream expression and neuroinflammation inhibition was caused by tumor-derived DNA. However, DMXAA reversed the STING siRNA effect and increased neuroinflammation. α-Cyperone takes inhibitory effects on tumor-derived DNA that trigger microglia by STING pathway.
Conclusions:
α-Cyperone inhibition by tumor-derived DNA activated microglial to neuroinflammation in STING signaling pathway.
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