GGC represses activation of kinases controlling STAT3 phosphorylation.
As STAT3 can be activated by upstream kinases, we deciphered the actions of GGC on the phosphorylation of JAK1, JAK2, and Src. GGC inhibited p-JAK1, p-JAK2, and p-Src levels (Fig. 1F) without altering total JAK1, JAK2, and Src proteins. We also found that IL-6 promoted phosphorylation of STAT3 was maximally induced at 15 min after IL-6 treatment (Fig. 2A). As shown Fig. 2B and 2C, GGC attenuated IL-6-driven STAT3 phosphorylation and upstream signaling proteins in time dependent manner. In addition, H1299 cells were transfected with STAT3-luciferase construct and when the cells exposed to GGC prior to stimulation, IL-6-induced STAT3 activity was repressed significantly.