UC San Diego

Janus kinase 2 (JAK2) is a signal transducer and activator of transcription (STAT3) pathway is known to be involved in the development and progression of different types of cancers, including gliomas. STAT3 is activated by the phosphorylation of tyrosine 705, after which it is dimerizes and translocates in to the nucleus of cancer cells. The STAT3 signaling cascade promotes several oncogenic signaling pathways, and recent studies reveal a correlation between STAT3 signaling and glioblastoma multiforme stem-like cell (GBM-SC) expansion. In the present study, we focused on a novel small molecule inhibitor TG101209, and examined its capacity to suppress STAT3 phosphorylation and the growth of human GBM neurospheres in vitro and in vivo. TG101209 potently inhibited STAT3 phosphorylation and inhibited cell proliferation (IC50 1-10 [mu]M), down regulated Bcl-Xl and induced PARP cleavage to induce apoptosis in GBM neurospheres. We conclude that TG101209 potently inhibits STAT3, and may have therapeutic potential for GBM expressing JAK2