Dataset Information

The ?-3 epoxide of eicosapentaenoic acid inhibits endothelial cell proliferation by p38 MAP kinase activation and cyclin D1/CDK4 down-regulation.

ABSTRACT: BACKGROUND AND PURPOSE: Dietary intake of ?-3 polyunsaturated fatty acids (?-3 PUFAs) like eicosapentaenoic acid (EPA) decreases cancer risk, while arachidonic acid and other ?-6 PUFAs increase risk, but the underlying mechanisms are unclear. Cytochrome P450 (CYP)-derived epoxides contribute to enhanced tumourigenesis due to ?-6 PUFA intake. Thus, ?-6 arachidonic acid epoxides (EETs) inhibit apoptosis and stimulate proliferation by up-regulating cyclin D1 expression in cells. The present study evaluated the corresponding ?-3 PUFA epoxides and assessed their role in the regulation of cell proliferation. EXPERIMENTAL APPROACH: Four chemically stable EPA epoxides (formed at the 8,9-, 11,12-, 14,15- and 17,18-olefinic bonds) were synthesized and tested against growth-related signalling pathways in brain microvascular endothelial bEND.3 cells. Cell cycle distribution was determined by flow cytometry and cyclin gene expression by immunoblotting and real-time PCR. The role of the p38 mitogen-activated protein (MAP) kinase in cyclin D1 dysregulation was assessed using specific inhibitors and dominant-negative expression plasmids. KEY RESULTS: The ?-3 17,18-epoxide of EPA decreased cell proliferation, interrupted the cell cycle in S-phase and down-regulated the cyclin D1/cyclin-dependent kinase (CDK)-4 complex, whereas the 8,9-, 11,12- and 14,15-epoxides were either inactive or enhanced proliferation. Cyclin D1 down-regulation by 17,18-epoxy-EPA was mediated by activation of the growth-suppressing p38 MAP kinase, but the alternate EPA-epoxides were inactive. CONCLUSIONS AND IMPLICATIONS: The present findings suggest that the epoxide formed by CYP enzymes at the ?-3 olefinic bond may contribute to the beneficial effects of ?-3 PUFA by down-regulating cyclin D1 and suppressing cell proliferation.

SUBMITTER: Cui PH

PROVIDER: S-EPMC3051386 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The ω-3 epoxide of eicosapentaenoic acid inhibits endothelial cell proliferation by p38 MAP kinase activation and cyclin D1/CDK4 down-regulation.

Cui Pei H PH Petrovic Nenad N Murray Michael M

British journal of pharmacology 20110301 5

<h4>Background and purpose</h4>Dietary intake of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) like eicosapentaenoic acid (EPA) decreases cancer risk, while arachidonic acid and other ω-6 PUFAs increase risk, but the underlying mechanisms are unclear. Cytochrome P450 (CYP)-derived epoxides contribute to enhanced tumourigenesis due to ω-6 PUFA intake. Thus, ω-6 arachidonic acid epoxides (EETs) inhibit apoptosis and stimulate proliferation by up-regulating cyclin D1 expression in cells. The present ...[more]

PMID: 21077851

Similar Datasets

Project description:BACKGROUND:Cyclic RNA (circRNA) is a new type of non-coding RNA (ncRNA) which is different from traditional linear RNA. More and more studies suggest that circRNA can be used as a biological marker of many malignant tumors and becomes a potential target for treatment. Therefore, searching for new molecular targets of lung adenocarcinoma from the circRNA will help to reveal the new mechanism of the occurrence and development of lung adenocarcinoma, and provide new ideas for clinical diagnosis and treatment. In this study, the biological function of circ_0007766, a highly expressed circRNA found in a screen of lung adenocarcinoma tissue, was verified and analyzed in vitro, so as to preliminarily explore the mechanism of circ_0007766 in promoting the proliferation of lung adenocarcinoma. METHODS:The expression level of circ_0007766 in lung adenocarcinoma cells was detected by qPCR. Then siRNA was used to knock down the expression of circ_0007766. The effects of knockdown of circ_0007766 on proliferation, cell cycle and apoptosis of lung adenocarcinoma cells were detected by CCK8, scratch test, PI staining and Annexin V/PI double staining. In addition, the biological mechanism of circ_0007766 in lung adenocarcinoma was preliminarily studied by qPCR and Western blots. RESULTS:The expression of circ_0007766 in lung adenocarcinoma cell lines was detected by qPCR. The expression of circ_0007766 was interfered in SPCA-1 cells. The proliferation and migration abilities of cells were inhibited. The cell cycle was arrested in G0/G1 phase, but the apoptosis was not affected. The deletion of circ_0007766 did not affect the expression of ERBB2, but influenced the mRNA and protein expression of Cyclin D1/Cyclin E1/CDK4. CONCLUSIONS:In vitro functional studies have shown that circ_0007766 may promote the proliferation and migration of lung adenocarcinoma cells. Further molecular mechanism studies have found that circ_0007766 can up-regulate the expression of Cyclin D1/Cyclin E1/CDK4, which are the key proteins of cell cycle, and thus promote the malignant proliferation of lung adenocarcinoma. From the perspective of circRNA, this study will provide new clues for the pathogenesis, development and prognosis of lung adenocarcinoma, and provide new target for clinical treatment.

Dataset Information

The ?-3 epoxide of eicosapentaenoic acid inhibits endothelial cell proliferation by p38 MAP kinase activation and cyclin D1/CDK4 down-regulation.

Publications

The ω-3 epoxide of eicosapentaenoic acid inhibits endothelial cell proliferation by p38 MAP kinase activation and cyclin D1/CDK4 down-regulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure