Asthma is a common chronic inflammatory disease whose pathogenesis has been attributed to multiple cell types. Due to the ability to suppress multiple inflammatory genes that contribute to asthma, corticosteroids have long been important drugs for asthma therapy. However, their beneficial effects do not apply to all patients suggesting the need for novel and potent immunosuppressant agents. CP690550 ( egfr inhibitors) (Fig. 1) is a small molecule inhibitor of JAK with an IC50 estimated at 0.2 M for PV patient progenitor cells. Enzymatic assays indicate that both JAK1 and JAK2 are 100 and 20 fold less sensitive to inhibition by CP690550, respectively, when compared with JAK3. Currently, the most studied pathway in MM is possibly the role of IL6 and its subsequent activation of JAK/STAT. Probably because some human myeloma cell lines (HMCL) cannot proliferate or survive without exogenous IL6, and the presence of IL6 can make HMCL insensitive to some conventional drugs. CYT387 is a novel ATP competitive small molecule JAK1/JAK2/JAK3 inhibitor with IC50 of 11, 18 and 160 nM for JAK1, JAK2 and JAK3, respectively. Fig. 1 Structure of CP690550 As early as 2004, Chatila' paper has shown that JAK3 inhibition might affect the function of some cytokines implicated in allergic airway disease, including IL4[1]. In recent study, Kudlacz' group confirmed CP690550' ability to inhibit IL4 mediated effects using murine B cells in vitro. The IC50 for inhibition of these IL4 mediated responses by CP690550 was 70.74.33 nM (MHCII) and 57.014.4 nM (CD23)[2]. Further work indicated that CUDC-101 inhibited murine eosinophilia more potently than the comparative agents, tacrolimus and produced a maximum effect slightly less than that of another control, dexamethasone [2]. Thus, CP690550 may represent an novel therapy for treatment of allergic inflammation including asthma and rhinitis. In a recent paper, Yu et al [1] reported the anti cancer mechanismof fucoxanthin in MGC 803 cells, a kind of human gastric adenocarcinoma cells. Fluorescence microscope and flow cytometry showed that fucoxanthin induced apoptosis of MGC803 cells and inhibited proliferation of MGC 803 cells. Previous studies also have shown the growth inhibitory effects on other cell lines such as those of prostate cancer, colon cancer [2], hepatic cancer [3]. Asmentioned previously, the development of gastric cancer has been closely related to JAK/STAT pathway. Among all STATs, STAT3 played an important role during the activation of JAK/STAT pathway while AG490 (inhibitor of JAK kinase) can block JAK/STAT pathway effectively. The expression of STAT3 were reduced by fucoxanthinat both on mRNA and protein level suggesting the inhibiting effects on JAK/STAT pathway of fucoxanthin. At the presence of AG490, the expressions of p STAT3 and survivin were also reduced to a level slightly lower. With the co treatment of fucoxanthin and AG490, the reduction expressions of STAT3, pSTAT3 and CyclinB1 by fucoxanthin was inhibited. Reference [1]. Chatila, T.A. 2004. Interleukin4 receptor signaling pathways in asthma pathogenesis. Trends Mol Med. 10, 493""499. [2]. Kudlacz, E., et al. 2008. The JAK-3 inhibitor CP690550 is a potent anti-inflammatory agent in a murine model of pulmonary eosinophilia. Eur J Pharmacol. 582, 154""161.
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