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

doi:10.1016/j.canlet.2010.10.004

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 journal › Article › peer-review

116 Scopus citations

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 language	English (US)
Pages (from-to)	180-188
Number of pages	9
Journal	Cancer Letters
Volume	300
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2010.10.004
State	Published - Jan 28 2011

Keywords

Angiogenesis
Chemokine
Colon cancer
Metastasis

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2010.10.004

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title = "Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases",

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.",

keywords = "Angiogenesis, Chemokine, Colon cancer, Metastasis",

author = "Varney, {Michelle L.} and Seema Singh and Aihua Li and Rosemary Mayer-Ezell and Richard Bond and Singh, {Rakesh K.}",

note = "Funding Information: This work was supported in part by Grants CA72781 (R.K.S.), and Cancer Center Support Grant (P30CA036727) from National Cancer Institute, National Institutes of Health and Nebraska Research Initiative Cancer Glycomics Program (R.K.S.) and Schering-Plough Research Institute.",

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doi = "10.1016/j.canlet.2010.10.004",

language = "English (US)",

volume = "300",

pages = "180--188",

journal = "Cancer Letters",

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number = "2",

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TY - JOUR

T1 - Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases

AU - Varney, Michelle L.

AU - Singh, Seema

AU - Li, Aihua

AU - Mayer-Ezell, Rosemary

AU - Bond, Richard

AU - Singh, Rakesh K.

N1 - Funding Information: This work was supported in part by Grants CA72781 (R.K.S.), and Cancer Center Support Grant (P30CA036727) from National Cancer Institute, National Institutes of Health and Nebraska Research Initiative Cancer Glycomics Program (R.K.S.) and Schering-Plough Research Institute.

PY - 2011/1/28

Y1 - 2011/1/28

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Chemokine

KW - Colon cancer

KW - Metastasis

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SN - 0304-3835

VL - 300

SP - 180

EP - 188

JO - Cancer Letters

JF - Cancer Letters

IS - 2

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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