A novel small molecule inhibits STAT3 phosphorylation and DNA binding activity and exhibits potent growth suppressive activity in human cancer ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-08-16

AUTHORS

Li Lin, Stephanie Deangelis, Elizabeth Foust, James Fuchs, Chenglong Li, Pui-Kai Li, Eric B Schwartz, Gregory B Lesinski, Don Benson, Jiagao Lü, Dale Hoyt, Jiayuh Lin

ABSTRACT

BackgroundTargeting Signal Transducer and Activator of Transcription 3 (STAT3) signaling is an attractive therapeutic approach for most types of human cancers with constitutively activated STAT3. A novel small molecular STAT3 inhibitor, FLLL32 was specifically designed from dietary agent, curcumin to inhibit constitutive STAT3 signaling in multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cells.ResultsFLLL32 was found to be a potent inhibitor of STAT3 phosphorylation, STAT3 DNA binding activity, and the expression of STAT3 downstream target genes in vitro, leading to the inhibition of cell proliferation as well as the induction of Caspase-3 and PARP cleavages in human multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cell lines. However, FLLL32 exhibited little inhibition on some tyrosine kinases containing SH2 or both SH2 and SH3 domains, and other protein and lipid kinases using a kinase profile assay. FLLL32 was also more potent than four previously reported JAK2 and STAT3 inhibitors as well as curcumin to inhibit cell viability in these cancer cells. Furthermore, FLLL32 selectively inhibited the induction of STAT3 phosphorylation by Interleukin-6 but not STAT1 phosphorylation by IFN-γ.ConclusionOur findings indicate that FLLL32 exhibits potent inhibitory activity to STAT3 and has potential for targeting multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cells expressing constitutive STAT3 signaling. More... »

PAGES

217

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1476-4598-9-217

DOI

http://dx.doi.org/10.1186/1476-4598-9-217

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052907373

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20712901


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