Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function

Ian S. Zagon, Renee N. Donahue, Moshe Rogosnitzky, Patricia J. McLaughlin

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The imidazoquinoline compounds imiquimod and resiquimod are low-molecular-weight immune response modifiers that have potent anti-viral and anti-tumor properties. The mechanism by which they exert their effects remains unclear. Using pancreatic and colorectal cancer cells, as well as squamous carcinoma cells of the head and neck in tissue culture, which eliminated the immune system and toll-like receptors, we show that the imidazoquinolines upregulate the Opioid Growth Factor receptor (OGFr), which in turn stimulates the interaction of the OGF-OGFr axis. This native, tonically active inhibitory pathway regulates cell proliferation by modulating cyclin dependent kinase inhibitors, resulting in a retardation of cells at the G1-S interface of the cell cycle. Neutralization of OGF or knockdown of OGFr by siRNA technology eliminates the inhibitory effects of imidazoquinolines on cell replication. This exciting new knowledge of the mechanism of imidazoquinolines has important physiological relevance, and allows strategies to be developed for the use of these agents that will enhance effectiveness as well as attenuate side-effects.

Original languageEnglish (US)
Pages (from-to)968-979
Number of pages12
JournalExperimental Biology and Medicine
Volume233
Issue number8
DOIs
StatePublished - Aug 1 2008

Fingerprint

imiquimod
Cell proliferation
Up-Regulation
Cell Proliferation
resiquimod
Cells
Tissue culture
Cyclin-Dependent Kinases
Immune system
Toll-Like Receptors
Pancreatic Neoplasms
Small Interfering RNA
Tumors
Colorectal Neoplasms
Immune System
Cell Cycle
Molecular Weight
Molecular weight
Technology
methionine-enkephalin receptor

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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Imiquimod upregulates the opioid growth factor receptor to inhibit cell proliferation independent of immune function. / Zagon, Ian S.; Donahue, Renee N.; Rogosnitzky, Moshe; McLaughlin, Patricia J.

In: Experimental Biology and Medicine, Vol. 233, No. 8, 01.08.2008, p. 968-979.

Research output: Contribution to journalArticle

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