New Cancer Gene Therapy Study Findings Have Been Reported from Beckman Research Institute (Dual inhibition of Janus and Src family kinases by novel indirubin derivative blocks constitutively-activated Stat3 signaling associated with apoptosis ...)
By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- Current study results on Biotechnology have been published. According to news originating from Duarte, California, by NewsRx correspondents, research stated, "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."
Our news journalists obtained a quote from the research from Beckman Research Institute, "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 and SFKs in vitro are in the ranges of 0.7-74.1 nM and 10.7-263.9 nM, respectively. We observed that phosphorylation of both Jak2 and Src was substantially inhibited in the submicromolar range by E738 in cultured human pancreatic tumor cells, followed by blockade of downstream Stat3 activation. E738 down-regulated expression of the Stat3 target proteins Mcl-1 and survivin, associated with induction of apoptosis. Computational models and molecular dynamics simulations of E738/Tyk2 or E738/Src in silico suggest that E738 inhibits both tyrosine kinase 2 (Tyk2) and Src as an ATP-competitive ligand. Moreover, the planar E738 molecule demonstrates a strong binding affinity in the compact ATP-binding site of Tyk2. In sum, E738 is the first dual inhibitor of JAKs and SFKs, followed by inhibition of Stat3 signaling."
According to the news editors, the research concluded: "Thus, according to in vitro experiments, E738 is a promising new therapeutic agent for human pancreatic cancer treatment by blocking both oncogenic pathways simultaneously."
For more information on this research see: 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. Molecular Oncology, 2013;7(3):369-78. (Elsevier - www.elsevier.com; Molecular Oncology - www.elsevier.com/wps/product/cws_home/709916)
The news correspondents report that additional information may be obtained from S. Nam, Molecular Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, United States. Additional authors for this research include W. Wen, A. Schroeder, A. Herrmann, H. Yu, X. Cheng, K.H. Merz, G. Eisenbrand, H. Li, Y.C. Yuan and R. Jove (see also Biotechnology).
Keywords for this news article include: Biotechnology, Duarte, Oncology, Apoptosis, California, United States, Gastroenterology, Pancreatic Cancer, Cancer Gene Therapy, Pancreatic Neoplasms, North and Central America.
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