A new class of inhibitors of 2-arachidonoylglycerol hydrolysis and invasion of prostate cancer cells

Kasem Nithipatikom, Michael P. Endsley, Marilyn A. Isbell, Craig E. Wheelock, Bruce D. Hammock, William B. Campbell

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Endogenous 2-arachidonoylglycerol (2-AG) inhibits invasion of androgen-independent prostate cancer cells. Blocking cellular hydrolysis of 2-AG to increase its endogenous concentration results in a decrease in cell invasion. A series of compounds containing a trifluoromethyl ketone (TFK) moiety or the methyl analog (known to inhibit carboxylesterases) were investigated for their ability to inhibit 2-AG hydrolysis and prostate cancer cell invasion. Compounds containing a thioether β to a TFK moiety inhibited 2-AG hydrolysis as well as cell invasion in a concentration-dependent manner. Inhibition of 2-AG hydrolysis increased concomitantly with inhibitor alkyl chain length from 4- to 12-carbons while inhibition of cell invasion exhibited a maximum at 8- to 10-carbons of the compounds. These results demonstrate a new series of 2-AG hydrolysis inhibitors as a potential therapeutic approach for prostate cancer.

Original languageEnglish (US)
Pages (from-to)1028-1033
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume332
Issue number4
DOIs
StatePublished - Jul 15 2005

Keywords

  • 2-Arachidonoylglycerol
  • Carboxylesterase inhibitors
  • Cell invasion
  • Endocannabinoid
  • Prostate cancer

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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    Nithipatikom, K., Endsley, M. P., Isbell, M. A., Wheelock, C. E., Hammock, B. D., & Campbell, W. B. (2005). A new class of inhibitors of 2-arachidonoylglycerol hydrolysis and invasion of prostate cancer cells. Biochemical and Biophysical Research Communications, 332(4), 1028-1033. https://doi.org/10.1016/j.bbrc.2005.05.049