Chemoresistance is a major problem in the treatment of patients with multiple myeloma(MM). Interleukin 6(IL-6), the most important growth factor for myeloma cells, mediates multiple signals which play a central role not only in the cell survival and the proliferation but also in the chemoresistance. The agents that suppress the IL-6-mediated signaling have the potential for the treatment of MM, such as PS-341 and curcumin. We have previously shown that baicalein from Scutellaria radix inhibited the proliferation and induced apoptosis of human myeloma cells, partly due to the suppression of IkB phosphorylation, resulting in the downregulation of NF-kB activity (

Blood 105:3312,2005
). In order to clarify whether baicalein could inhibit IL-6-triggered signaling cascades in myeloma cells, we first demonstrated that baicalein inhibited not only the activation of MAPK, but also the phosphorylation of Stat3 and Stat1 induced by IL-6. Baicalein could also inhibit the phosphorylation of Akt triggered by IL-6, but not IGF-1. Since gp130 is phosphorylated by Jak family kinase after IL-6 stimulation, we examined whether Jak kinases could be involved in the baicalein-induced blockade of IL-6-induced signaling mediating the survival and growth of myeloma cells and the drug-resistance. Furthermore, we showed by phosphoprotein immunoblotting analysis that baicalein inhibited the activity of Jak2 and Tyk2 in myeloma cell lines (U266 and NOP-2 cells). Therefore, our results indicate that baicalein can also inhibit IL-6-induced signaling through Jak family kinase in myeloma cells, and combined with its suppressive effect on NF-kB activity baicalein can lead to more effective suppression of the proliferation and survival of myeloma cells.

Topics:
myeloma cells, phosphotransferases, signal transduction, interleukin-6, nf-kappa b, curcumin, growth factor, i-kappa b proteins, immunoblotting, insulin-like growth factor i

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2005, The American Society of Hematology
2005
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