Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases

Michelle L. Varney, Seema Singh, Aihua Li, Rosemary Mayer-Ezell, Richard Bond, Rakesh K Singh

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

CXCR1 and CXCR2 are G-protein coupled receptors, that have been shown to play important role in tumor growth and metastasis, and are prime targets for the development of novel therapeutics. Here, we report that targeting CXCR2 and CXCR1 activity using orally active small molecule antagonist (SCH-527123, SCH-479833) inhibits human colon cancer liver metastasis mediated by decreased neovascularization and enhanced malignant cell apoptosis. There were no differences in primary tumor growth. These studies demonstrate the important role of CXCR2/1 in colon cancer metastasis and that inhibition of CXCR2 and CXCR1, small molecule antagonists provides a novel therapeutic strategy.

Original languageEnglish (US)
Pages (from-to)180-188
Number of pages9
JournalCancer Letters
Volume300
Issue number2
DOIs
StatePublished - Jan 28 2011

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Liver Neoplasms
Colonic Neoplasms
Neoplasm Metastasis
Interleukin-8B Receptors
Growth
G-Protein-Coupled Receptors
Neoplasms
Apoptosis
Therapeutics

Keywords

  • Angiogenesis
  • Chemokine
  • Colon cancer
  • Metastasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases. / Varney, Michelle L.; Singh, Seema; Li, Aihua; Mayer-Ezell, Rosemary; Bond, Richard; Singh, Rakesh K.

In: Cancer Letters, Vol. 300, No. 2, 28.01.2011, p. 180-188.

Research output: Contribution to journalArticle

Varney, Michelle L. ; Singh, Seema ; Li, Aihua ; Mayer-Ezell, Rosemary ; Bond, Richard ; Singh, Rakesh K. / Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases. In: Cancer Letters. 2011 ; Vol. 300, No. 2. pp. 180-188.
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