Dual inhibition of cyclooxygenase-2 and soluble epoxide hydrolase synergistically suppresses primary tumor growth and metastasis

Details

• Personal Author:
  Ferrara KW ; Hammock BD ; Hwang SH ; Ingham ES ; Kieran MW ; Liu J-Y ; Mahakian LM ; Panigrahy D ; Tam S ; Wang Y ; Weiss RH ; Wettersten HI ; Yang J ; Zhang G
• Description:
  Prostaglandins derived from the cyclooxygenase (COX) pathway and epoxyeicosatrienoic acids (EETs) from the cytochrome P450/soluble epoxide hydrolase (sEH) pathway are important eicosanoids that regulate angiogenesis and tumorigenesis. COX-2 inhibitors, which block the formation of prostaglandins, suppress tumor growth, whereas sEH inhibitors, which increase endogenous EETs, stimulate primary tumor growth and metastasis. However, the functional interactions of these two pathways in cancer are unknown. Using pharmacological inhibitors as probes, we show here that dual inhibition of COX-2 and sEH synergistically inhibits primary tumor growth and metastasis by suppressing tumor angiogenesis. COX-2/sEH dual pharmacological inhibitors also potently suppress primary tumor growth and metastasis by inhibiting tumor angiogenesis via selective inhibition of endothelial cell proliferation. These results demonstrate a critical interaction of these two lipid metabolism pathways on tumorigenesis and suggest dual inhibition of COX-2 and sEH as a potential therapeutic strategy for cancer therapy. [Description provided by NIOSH]
• Subjects:
  Biopharmaceutics Carcinogens Cytology Enzymes Histocytochemistry Lipids Neoplasms Occupational Health Safety
• Keywords:
  Cell-alteration Cell-metabolism Cytochemistry Enzyme-activity Fatty-acids Pharmaceuticals Pharmacodynamics Prostaglandin-inhibitors Tumor-inhibition Tumorigenesis Tumors

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• ISSN:
  0027-8424
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  California ; Massachusetts ; OSHA Region 1 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  111
• Issue:
  30
• NIOSHTIC Number:
  nn:20044747
• Citation:
  Proc Natl Acad Sci U.S.A. 2014 Jul; 111(30):11127-11132
• Contact Point Address:
  Bruce D. Hammock, Department of Entomology and Nematology and Comprehensive Cancer Center, University of California, Davis, CA 95616
• Email:
  bdhammock@ucdavis.edu
• Federal Fiscal Year:
  2014
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of California - Davis
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Proceedings of the National Academy of Sciences of the United States of America
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3c993440783ccd2c07bc1e439e06075420c58e62adee727f0574027fbc96088f48691a5fbe23fa51409e253f8248c1a6cd13a05ee9587281d69215649b872a0d
• Download URL:
  https://stacks.cdc.gov/view/cdc/200383/cdc_200383_DS1.pdf
• File Type:
  [PDF - 1.04 MB ]