Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: Modern target but ancient solution

Bharat B. Aggarwal, Gautam Sethi, Seok Ahn Kwang, Santosh K. Sandur, Manoj K. Pandey, Ajaikumar B. Kunnumakkara, Bokyung Sung, Haruyo Ichikawa

Research output: Chapter in Book/Report/Conference proceedingConference contribution

342 Scopus citations

Abstract

Recent evidence indicates a convergence of molecular targets for both prevention and therapy of cancer. Signal-transducer-and-activator-of- transcription-3 (STAT3), a member of a family of six different transcription factors, is closely linked with tumorigenesis. Its role in cancer is indicated by numerous avenues of evidence, including the following: STAT3 is constitutively active in tumor cells; STAT3 is activated by growth factors (e.g.,EGF, TGF-α, IL-6, hepatocyte growth factor) and oncogenic kinases (e.g., Src); STAT3 regulates the expression of genes that mediate proliferation (e.g., c-myc and cyclin D1), suppress apoptosis (e.g., Bcl-XL and survivin), or promote angiogenesis (e.g, VEGF); STAT3 activation has been linked with chemoresistance and radioresistance; and chemopreventive agents have been shown to suppress STAT3 activation. Thus inhibitors of STAT3 activation have potential for both prevention and therapy of cancer. Besides small peptides and oligonucleotides, numerous small molecules have been identified as blockers of STAT3 activation, including synthetic molecules (e.g., AG 490, decoy peptides, and oligonucleotides) and plant polyphenols (e.g., curcumin, resveratrol, flavopiridol, indirubin, magnolol, piceatannol, parthenolide, EGCG, and cucurbitacin). This article discusses these aspects of STAT3 in more detail.

Original languageEnglish (US)
Title of host publicationSignal Transduction Pathways, Part B
Subtitle of host publicationStress Signalling and Transcriptional Control
PublisherBlackwell Publishing Inc.
Pages151-169
Number of pages19
ISBN (Print)1573316474, 9781573316477
DOIs
StatePublished - Dec 2006

Publication series

NameAnnals of the New York Academy of Sciences
Volume1091
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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