Extracellular signal-regulated kinase is a target of cyclooxygenase-1- peroxisome proliferator-activated receptor-δ signaling in epithelial ovarian cancer

Takiko Daikoku, Susanne Tranguch, Anindita Chakrabarty, Dingzhi Wang, Dineo Khabele, Sandra Orsulic, Jason D. Morrow, Raymond N. DuBois, Sudhansu K. Dey

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The underlying causes of epithelial ovarian cancer (EOC) are unclear, and treatment options for patients with advanced disease are limited. There is evidence that the use of nonsteroidal anti-inflammatory drugs is associated with decreased risk of developing EOC. Nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase (COX)-1 and COX-2, which catalyze prostaglandin biosynthesis. We previously showed that mouse and human EOCs have increased levels of COX-1, but not COX-2, and a COX-1-selective inhibitor, SC-560, attenuates prostaglandin production and tumor growth. However, the downstream targets of COX-1 signaling in EOC are not yet known. To address this question, we evaluated peroxisome proliferator-activated receptor δ (PPARδ) expression and function in EOC. We found that EOC cells express high levels of PPARδ, and neutralizing PPARδ function reduces tumor growth in vivo. More interestingly, aspirin, a nonsteroidal anti-inflammatory drug that preferentially inhibits COX-1, compromises PPARδ function and cell growth by inhibiting extracellular signal-regulated kinases 1/2, members of the mitogen-activated protein kinase family. Our study, for the first time, shows that whereas PPARD can be a target of COX-1, extracellular signal-regulated kinase is a potential target of PPARδ. The ability of aspirin to inhibit EOC growth in vivo is an exciting finding because of its low cost, lack of cardiovascular side effects, and availability.

Original languageEnglish (US)
Pages (from-to)5285-5292
Number of pages8
JournalCancer Research
Volume67
Issue number11
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

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Cyclooxygenase 1
Peroxisome Proliferator-Activated Receptors
Extracellular Signal-Regulated MAP Kinases
Anti-Inflammatory Agents
Cyclooxygenase 2
Growth
Aspirin
Prostaglandins
Pharmaceutical Preparations
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinases
Ovarian epithelial cancer
Neoplasms
Costs and Cost Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Extracellular signal-regulated kinase is a target of cyclooxygenase-1- peroxisome proliferator-activated receptor-δ signaling in epithelial ovarian cancer. / Daikoku, Takiko; Tranguch, Susanne; Chakrabarty, Anindita; Wang, Dingzhi; Khabele, Dineo; Orsulic, Sandra; Morrow, Jason D.; DuBois, Raymond N.; Dey, Sudhansu K.

In: Cancer Research, Vol. 67, No. 11, 01.06.2007, p. 5285-5292.

Research output: Contribution to journalArticle

Daikoku, T, Tranguch, S, Chakrabarty, A, Wang, D, Khabele, D, Orsulic, S, Morrow, JD, DuBois, RN & Dey, SK 2007, 'Extracellular signal-regulated kinase is a target of cyclooxygenase-1- peroxisome proliferator-activated receptor-δ signaling in epithelial ovarian cancer', Cancer Research, vol. 67, no. 11, pp. 5285-5292. https://doi.org/10.1158/0008-5472.CAN-07-0828
Daikoku, Takiko ; Tranguch, Susanne ; Chakrabarty, Anindita ; Wang, Dingzhi ; Khabele, Dineo ; Orsulic, Sandra ; Morrow, Jason D. ; DuBois, Raymond N. ; Dey, Sudhansu K. / Extracellular signal-regulated kinase is a target of cyclooxygenase-1- peroxisome proliferator-activated receptor-δ signaling in epithelial ovarian cancer. In: Cancer Research. 2007 ; Vol. 67, No. 11. pp. 5285-5292.
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