Table 4 The involvement of 15-LOX and its metabolites in the pro-tumorigenic effects of various conjugated lipid-based diets in breast cancer; in vitro evidences
From: 15-Lipoxygenase and its metabolites in the pathogenesis of breast cancer: A double-edged sword
Type of 15-LOX enzyme/ metabolites examined | Cell line/Human tissue type/serum | Type of intervention | Observations | Ref |
|---|---|---|---|---|
PGE2 12-HETE 15-HETE | MDA-MB-435 cells | LA-enriched supplement | • linoleic acid-rich supplement stimulate production of PGE2, 12-HETE and 15-HETE which was associated with cell invasion. • Inhibition of 12-LOX abolish eicosanoid metabolites secretion, cell invasion and activate metalloproteinase-9 | [54] |
13-HODE 15(S)-HETE | Steroid receptor negative (SR2) MCF-7 | Linoleic acid isomers/13-HODE | • Uptake of linoleic acid, the content of cAMP and the activity of Erk1/2 and production of 13-HODE were inhibited following linoleic acid isomers administration. • linoleic acid isomers caused production of 15(S)-HETE in tumor tissue of MCF-7 (SR2) human breast xenografts. • 13-HODE synergize with linoleic acid to elevate cAMP level. | [56] |
15-HETE 5-HETE 12- HETE | MDA-MB-231 | Conjugated linoleic acid (CLA) | • CLA (t10, c12-CLA) reduced 15-HETE and 5-HETE level. • Arachidonic acid caused production of 15- HETE, 12- HETE and 5-HETE while incubated with cell extracted proteins. • 5-, 12- and 15-LOX-2 have minimum effect on metabolizing c9, t11-CLA or t10, c12-CLA in breast cancer. • 15-LOX-1 was not able to metabolize c9, t11-CLA or t10, c12-CLA isomers. | [52] |
15(S)-HETE 15-LOX-1 15-LOX-2 | MDA-MB-435 | Exogenous arachidonic acid/ exogenous 15(S)-HETE | • Exogenous arachidonic acid results in the production of 15(S)-HETE and phosphorylation of p38 MAPK that were abrogated following LOX inhibition. • Exogenous arachidonic acid induced protein expression of 15-LOX-2 but not 15-LOX-1. • Exogenous 15(S)-HETE activate p38 MAPK pathway and cell adhesion to type IV collagen | [60] |