12-HETE

12-HETE, a major metabolic product of arachidonic acid using 12-LOX catalysis, inhibits cell apoptosis in a dose-dependent manner. 12-HETE promotes the activation and nuclear translocation of NF-κB through the integrin-linked kinase (ILK) pathway[1].12-HETE has both anti-thrombotic and pro-thrombotic effects[2]. 12-HETE is a neuromodulator[3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cardiovascular Disease

Research Areas >> Inflammation/Immunology

12-HETE participates in the inhibition of cell apoptosis by activating the ILK/NF-κB pathway, implying an important underlying mechanism that promotes the survival of ovarian cancer cells. 12-HETE facilitates cell survival by activating the integrin-linked kinase/NF-κB pathway in ovarian cancer. 12-HETE protects against cell apoptosis in ovarian cancer cells in a concentration-dependent manner. 12-HETE (1 µM) significantly decreases the activation of caspase-3 induced by serum deprivation (SD).12-HETE represses the increased activity of caspase-3 induced by SD in a concentration-dependent manner, with an IC50 value of 1.13 µM[1]. 12-HETE (1 µM) facilitates the activation and nuclear translocation of NF-κB via ILK in ovarian cancer cells[1]. 12-HETE inhibits insulin secretion, reduces metabolic activity and induces cell death in human islets. 12-HETE increases bovine platelet aggregation induced by thrombin and inhibits prostaglandin E1-induced elevation of intracellular cAMP levels. 12-HETE inhibits washed platelet (WP) aggregation[2]. The neuronal effects of 12-HETE include attenuation of calcium influx and glutamate release as well as inhibition of AMPA receptor (AMPA-R) activation[3]. Cell Viability Assay[1] Cell Line: Ovarian cancer OVCAR-3 and SKOV3 cells Concentration: 0, 0.2, 0.5, and 1 µM Incubation Time: 0, 24, 48, 72, and 96 hours Result: Inhibited the decrease in cell viability induced by SD in a dose-dependent manner. 1 µM 12-HETE treatment significantly mitigated the decrease in cell viability under conditions of SD. Western Blot Analysis[1] Cell Line: Ovarian cancer OVCAR-3 and SKOV3 cells Concentration: 1 µM Incubation Time: Result: Led to increased levels of NF-κB p65 phosphorylation. Caused a significant increase in the protein levels of nuclear NF-κB p65, which was accompanied by decreased levels of NF-κB p65 in the cytoplasm.

[1]. Qian Liu, et al. 12-HETE facilitates cell survival by activating the integrin-linked kinase/NF-κB pathway in ovarian cancer. Cancer Manag Res. 2018 Nov 16;10:5825-5838.

[2]. Benedetta Porro, et al. Analysis, physiological and clinical significance of 12-HETE: a neglected platelet-derived 12-lipoxygenase product. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Aug 1;964:26-40.

[3]. Aidan J Hampson, et al. 12-hydroxyeicosatetrenoate (12-HETE) attenuates AMPA receptor-mediated neurotoxicity: evidence for a G-protein-coupled HETE receptor. J Neurosci. 2002 Jan 1;22(1):257-64.

MOLECULAR FORMULA :

C20-H32-O3

MOLECULAR WEIGHT :

320.52

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

MUTATION DATA

TYPE OF TEST :

DNA inhibition

TEST SYSTEM :

Human Cells - not otherwise specified

DOSE/DURATION :

20 umol/L

REFERENCE :

CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 45,561,1985