A small molecule compound targeting STAT3 DNA-binding domain inhibits cancer cell proliferation, migration, and invasion

Wei Huang, Zizheng Dong, Fang Wang, Hui Peng, Jing Yuan Liu, Jian-Ting Zhang

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Signal transducer and activator of transcription 3 (STAT3) plays important roles in multiple aspects of cancer aggressiveness including migration, invasion, survival, self-renewal, angiogenesis, and tumor cell immune evasion by regulating the expression of multiple downstream target genes. STAT3 is constitutively activated in many malignant tumors and its activation is associated with high histological grade and advanced cancer stages. Thus, inhibiting STAT3 promises an attracting strategy for treatment of advanced and metastatic cancers. Herein, we identified a STAT3 inhibitor, inS3-54, by targeting the DNA-binding domain of STAT3 using an improved virtual screening strategy. InS3-54 preferentially suppresses proliferation of cancer over non-cancer cells and inhibits migration and invasion of malignant cells. Biochemical analyses show that inS3-54 selectively inhibits STAT3 binding to DNA without affecting the activation and dimerization of STAT3. Furthermore, inS3-54 inhibits expression of STAT3 downstream target genes and STAT3 binding to chromatin in situ. Thus, inS3-54 represents a novel probe for development of specific inhibitors targeting the DNA-binding domain of STAT3 and a potential therapeutic for cancer treatments.

Original languageEnglish
Pages (from-to)1188-1196
Number of pages9
JournalACS Chemical Biology
Volume9
Issue number5
DOIs
StatePublished - May 16 2014

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STAT3 Transcription Factor
Cell proliferation
Cell Movement
Cell Proliferation
Molecules
DNA
Neoplasms
Tumors
Genes
Chemical activation
Cells
Tumor Escape
Oncology
Dimerization
Chromatin
Screening

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Medicine(all)

Cite this

A small molecule compound targeting STAT3 DNA-binding domain inhibits cancer cell proliferation, migration, and invasion. / Huang, Wei; Dong, Zizheng; Wang, Fang; Peng, Hui; Liu, Jing Yuan; Zhang, Jian-Ting.

In: ACS Chemical Biology, Vol. 9, No. 5, 16.05.2014, p. 1188-1196.

Research output: Contribution to journalArticle

Huang, Wei ; Dong, Zizheng ; Wang, Fang ; Peng, Hui ; Liu, Jing Yuan ; Zhang, Jian-Ting. / A small molecule compound targeting STAT3 DNA-binding domain inhibits cancer cell proliferation, migration, and invasion. In: ACS Chemical Biology. 2014 ; Vol. 9, No. 5. pp. 1188-1196.
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