Dual inhibition of Janus and Src family kinases by novel indirubin derivative blocks constitutively-activated Stat3 signaling associated with apoptosis of human pancreatic cancer cells.

ABSTRACT: Constitutively-activated JAK/Stat3 or Src/Stat3 signaling plays a crucial role in tumor cell survival, proliferation, angiogenesis and immune suppression. Activated JAK/Stat3 or Src/Stat3 has been validated as a promising molecular target for cancer therapy. However, prolonged inhibition of Src family kinases (SFKs) leads to reactivation of signal transducer and activator of transcript 3 (Stat3) and tumor cell survival through altered JAK/Stat3 interaction. This compensatory feedback suggests that dual inhibition of Janus kinases (JAKs) and SFKs might be a promising strategy for targeting downstream Stat3 signaling in the clinic. In this study, we identify that the natural product derivative E738 is a novel dual inhibitor of JAKs and SFKs. The IC(50) values of E738 against recombinant JAKs

SUBMITTER: Nam S 

PROVIDER: S-EPMC3968804 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature