Inhibition of carcinoma cell motility by epoxyeicosatrienoic acid (EET) antagonists

Kasem Nithipatikom, Daniel M. Brody, Alan T. Tang, Vijaya L. Manthati, J R Falck, Carol L. Williams, William B. Campbell

Research output: Contribution to journalArticle

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Abstract

Cytochrome P450 (CYP) epoxygenases, CYP2C8, 2C9 and 2J2 mRNA and proteins, were expressed in prostate carcinoma (PC-3, DU-145 and LNCaP) cells. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the major arachidonic acid metabolite in these cells. Blocking EET synthesis by a selective CYP epoxygenase inhibitor (N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide [MS-PPOH]) inhibited tonic (basal) invasion and migration (motility) while exogenously added EET induced cell motility in a concentration-dependent manner. An epidermal growth factor receptor (EGFR) kinase inhibitor (AG494) or a PI3 kinase inhibitor (LY294002) inhibited cell migration and reduced 11,12-EET-induced cell migration. Importantly, synthetic EET antagonists (14,15-epoxyeicosa-5(Z)-enoic acid [14,15-EEZE], 14,15-epoxyeicosa-5(Z)-enoic acid 2-[2-(3-hydroxy-propoxy)-ethoxy]-ethyl ester [14,15-EEZE-PEG] and 14,15-epoxyeicosa-5(Z)-enoic-methylsulfonylimide [14,15-EEZE-mSI]) inhibited EET-induced cell invasion and migration. 11,12-EET induced cell stretching and myosin-actin microfilament formation as well as increased phosphorylation of EGFR and Akt (Ser473), while 14,15-EEZE inhibited these effects. These results suggest that EET induce and EET antagonists inhibit cell motility, possibly by putative EET receptor-mediated EGFR and PI3K/Akt pathways, and suggest that EET antagonists are potential therapeutic agents for prostate cancer. (Cancer Sci 2010; 101: 2629-2636)

Original languageEnglish (US)
Pages (from-to)2629-2636
Number of pages8
JournalCancer Science
Volume101
Issue number12
DOIs
StatePublished - Dec 2010

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Cell Movement
Carcinoma
Acids
Epidermal Growth Factor Receptor
Phosphatidylinositol 3-Kinases
Cytochrome P-450 Enzyme System
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Myosins
Actin Cytoskeleton
Arachidonic Acid
Prostate
Prostatic Neoplasms
Esters
Phosphorylation
14,15-episulfide eicosatrienoic acid
Messenger RNA
11,12-epoxy-5,8,14-eicosatrienoic acid
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nithipatikom, K., Brody, D. M., Tang, A. T., Manthati, V. L., Falck, J. R., Williams, C. L., & Campbell, W. B. (2010). Inhibition of carcinoma cell motility by epoxyeicosatrienoic acid (EET) antagonists. Cancer Science, 101(12), 2629-2636. https://doi.org/10.1111/j.1349-7006.2010.01713.x

Inhibition of carcinoma cell motility by epoxyeicosatrienoic acid (EET) antagonists. / Nithipatikom, Kasem; Brody, Daniel M.; Tang, Alan T.; Manthati, Vijaya L.; Falck, J R; Williams, Carol L.; Campbell, William B.

In: Cancer Science, Vol. 101, No. 12, 12.2010, p. 2629-2636.

Research output: Contribution to journalArticle

Nithipatikom, K, Brody, DM, Tang, AT, Manthati, VL, Falck, JR, Williams, CL & Campbell, WB 2010, 'Inhibition of carcinoma cell motility by epoxyeicosatrienoic acid (EET) antagonists', Cancer Science, vol. 101, no. 12, pp. 2629-2636. https://doi.org/10.1111/j.1349-7006.2010.01713.x
Nithipatikom, Kasem ; Brody, Daniel M. ; Tang, Alan T. ; Manthati, Vijaya L. ; Falck, J R ; Williams, Carol L. ; Campbell, William B. / Inhibition of carcinoma cell motility by epoxyeicosatrienoic acid (EET) antagonists. In: Cancer Science. 2010 ; Vol. 101, No. 12. pp. 2629-2636.
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