We revealed that cordycepin exhibited an anticancer action through the stimulation of adenosine A3 receptor followed by GSK-3β activation and cyclin D1 suppression (Fig. 1). Cordycepin also showed an antimetastatic action through the inhibition of platelet aggregation initiated by ADP released from cancer cells and reduction of the invasiveness selleck inhibitor of cancer cells via inhibiting the activity of MMP-2 and MMP-9 and accelerating the secretion of TIMP-1 and TIMP-2 from those cells (Fig. 2). Cordycepin, an active component of WECS, is expected to be a candidate anticancer

and antimetastatic agent. The authors declare no conflict of interest. This work was supported in part by a Grant-in-Aid for Scientific Research (C) (26460244) from the Japan Society for the Promotion of Science. “
“Increasing evidence http://www.selleckchem.com/products/AG-014699.html indicates that

inflammatory processes play important roles in the pathogenesis of many neurodegenerative disorders (1), (2) and (3). Under the neuroinflammatory conditions, it is known that the extracellular concentration of L-glutamate (L-Glu) and inflammatory mediators, such as proinflammatory cytokines, prostaglandins, free radicals and complements are elevated (4). L-Glu is one of the most abundant excitatory neurotransmitters in the mammalian CNS. The released L-Glu is immediately uptaken by astrocyte L-Glu transporters, GLAST (EAAT1 in human) and GLT-1 (EAAT2 in human), or sustained elevation of extracellular concentration of L-Glu induce excitotoxicity. The impairment of the astrocyte L-Glu transporters is reported in various neurological disorders including Alzheimer’s disease (5), Parkinson’s diseases (6) and amyotrophic lateral sclerosis (7). We found that the expression level of L-Glu transporters

in astrocytes of astrocyte-microglia-neuron mixed culture was decreased in the in vitro model of the early stage of inflammation in the previous study (8). We clarified the interaction between astrocytes and microglia underlie the down-regulation of L-Glu transporters, i.e., activated Tolmetin microglia release L-Glu and the resulting elevation of extracellular L-Glu cause down-regulation of astrocytic L-Glu transporters. Some antidepressants are known to have anti-inflammatory effects (9) and (10). In this study, therefore, we investigated the effects of various antidepressants on the decrease in the astrocytic L-Glu transporter function in the early stage of inflammation and the contribution of microglia to the effects. Astrocyte-microglia-neuron mixed culture and microglia culture were performed according to the methods previously described (8). Antidepressants and serotonin (5-HT) were dissolved in PBS at 100 μM and 10 mM, respectively, and were diluted with culture medium at the time of use. At 8 DIV, the astrocyte-microglia-neuron mixed culture was treated with 10 ng/mL LPS for 72 h. Antidepressants were applied from 1 h before to the end of the LPS-treatment.