Table 3 The involvement of 15-LOX and its metabolites in the pro-tumorigenic effects of various conjugated lipid-based diets in breast cancer; in vivo 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 |
|---|---|---|---|---|
PGE, 5-HETE 12-HETE 15-HETE | Nude mice tumor tissue | LA-enriched diet | • Indomethacin caused elevation in the level of PGE, 5-HETE, 12-HETE, and 15-HETE in tumors of the group under LA-enriched diet Indomethacin might reduce the risk of breast cancer progression in nude mice fed by LA-rich diet. | [53] |
LA-derived prostaglandin E2 12-HETE 15-HETE | MDA-MB-231 cell solid tumor | Docosahexaenoic acid diet containing 4% linoleic acid | • Inhibition of 15-HETE synthesis using docosahexaenoic acid administration caused reduced breast tumor cell growth, suppression of cell proliferation, increased apoptotic cells and inhibition of tumor-induced angiogenesis | [55] |
5-HETE 9-HODE 12-HETE 13-HODE | Rat breast tumors | CLA supplements | • CLA supplements induced production of 5-HETE, 9-HODE, 12-HETE and 13-HODE. • 5-HETE and 15-HETE in 7,12-dimethylbenz [a] anthracene (DMBA)-induced tumor group. • CLA- DMBA treated group induced low level of 13-HODE compared to oil-DMBA-treated group. | [58] |
LOX metabolites | Pregnant and breastfeeding female rats | CLA diet | • LOX metabolites of arachidonic acid (15-, 12-, 5-HETE) and linoleic acid (HODE) were higher in mammary tumors in groups under CLA diet. | [59] |
13-HODE | MCF-7 xenografts | Eicosapentaenoic acid (EPA) | • EPA inhibit proliferation of human MCF-7 xenografts through linoleic acid uptake and 13-HODE formation. • The lower level of 13-HODE was accompanied with decrease in cAMP and ERK1/2 phosphorylation. • Exogenous 13-HODE caused uptake of 13-HODE by tumors, increased the tumor DNA content, restored the phosphorylated ERK1/2. | [59] |
LA 13-HODE | MCF-7 human breast xenografts | melatonin (MLT), eicosapentaenoic acid (EPA), conjugated linoleic acid (CLA) | • Receiving anticancer agents (MLT, EPA, CLA) resulted in suppression of LA uptake, 13-HODE generation and phosphorylation of ERK1/2. | [62] |
Arachidonic acid (AA) content 15-LOX-1 15-LOX-2 | Murine mammary gland adenocarcinoma. | Peanut oil enriched diet rich in ω-3 and ω9 PUFAs | • Peanut oil enriched diet which is rich in ω-3 and ω9 PUFAs caused elevation of membrane AA content, reduced 15-LOX-2 and 15-LOX-1 activity, increased apoptosis, decrease mitosis. • Peanut oil enriched diet reduced tumor volume, number of metastasis and longer survival of rats. | [63] |