[Background] Cordyceps militaris is a traditional popular mushroom, produces an important bioactive compound Cordycepin (3’-deoxyadenosine) used for the tonic and medicinal purpose in eastern Asia. Cordycepin is reported to possess many pharmacological activities including immunologically stimulating, anti-tumor, anti-virus, and anti-infection effects. [Methods] Growth inhibition of human leukemia cells was assessed by MTT assays. The determination of apoptotic cell death was performed by flow cytometry analysis, agarose gel electrophoresis and DAPI fluorescent staining methods. The apoptotic-regulated gene markers in both death receptor- and mitochondria-mediated apoptotic pathways were detected by RT-PCR and Western blot analysis etc. [Results] It was found that inhibition of cell proliferation was observed for human leukemia U937 and THP-1 cells treated with cordycepin in a dose-dependent manner. Cordycepin induced morphological change and apoptotic cell death such as formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase. Apoptosis of U937 and THP-1 cells by cordycepin was associated with a down-regulation of anti-apoptotic Bcl-2 and inhibitor of apoptosis proteins (IAPs) expression. Cordycepin treatment induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant inhibition of poly(ADP-ribose) polymerase (PARP), β-catenin and phospholipase (PLC)-γ1 protein. Conclusions: Our results indicated that the apoptotic processes caused by cordycepin are mediated by the regulation of the Bcl-2 and caspase family in human leukemia U937 and THP-1 cells. Our data also suggested that cordycepin may be a potential chemotherapeutic agent for the treatment of leukemia cancer patients.

[Background] Cordyceps militaris, a traditional medicinal mushroom, produces a component compound, cordycepin (3’-deoxyadenosine). Cordycepin has been known to have many pharmacological activities including immunological stimulating, anti-cancer, and anti-infection activities. However, the molecular mechanisms of inflammatory mediator’s activity by cordycepin remain poorly understood. In the present study, we investigat-ed the effects of cordycepin on the anti- inflammation cascades in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. [Methods] Cordycepin were administered and their effects on LPS-induced pro-inflammatory mediators and MAP kinases were monitored by Western blotting and RT-PCR analysis. [Result] Cordycepin significantly inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), and pro- inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in a concentration- dependent manner without causing cytotoxicity. Also, cordycepin suppressed inducible NO, synthase (iNOS) and cyclooxygenase-2 (COX-2) expression on the mRNA and protein level. In addition, cordycepin suppressed NF-κB translocation by blocking IkappaB- α (IκB-α) degradation and inhibited the phosphorylation of Akt, ERK-1/2, JNK, and p38 kinase. Our results indicate that the inhibitory effect of cordycepin on LPS -stimulated inflammatory mediator production in BV2 microglia is associated with the suppression of the NF-κB, Akt, and MAPK signaling pathways. Conclusion: Anti-inflammatory properties of cordycepin may be useful for treating the inflammatory and deleterious effects of microglial activation in response to LPS stimulation.