Table 5 The effects of 15-LOX and its metabolites in breast cancer metastasis and invasion
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 treatment | Observations | Ref |
|---|---|---|---|---|
15-LOX-1 | MCF7/ endothelial monolayers | 15-LOX-1 activation 15-LOX-1 inhibition | • 15-LOX-1 gene activation induced in MCF7 cell spheroids. • 15-LOX-1 inhibition/knock-down leads to MCF7 spheroid–induced circular defects in lymphatic endothelial cell monolayers decrease. • 15-LOX-1 knock-down suppress formation of circular defects and metastasis to the lymph node in breast xenograft tumors. | [68] |
15-LOX-1 12(S)-HETE | MCF-7 | 15-LOX-1 inhibition | • 15-LOX-1 inhibition (baicalein) and NF-kB (Bay11–7082) caused inhibition of circular chemo repellent-induced defects’ (CCID) formation in MCF-7 cell spheroids. • 12(S)-HETE generation by 15-LOX-1 under NF-kB facilitate CCID and attachment of breast cancer cells to the lymph-endothelial cells. | [67] |
15(S)-HETE 13(S)-HODE | MCF-7 | Exposure to eicosapentaenoic (EPA), gamma linoleic acid (GLA) | • EPA treatment caused increased expression level of E-cadherin while GLA treatment had no effect. • GLA or EPA treatment caused elevation of 15(S)-HETE and 13(S)-HODE level | [69] |
15-LOX-1 | Myeloid derived suppressor cells (MDSCs), metastatic breast tumors |  | • In MDSCs from metastatic 4 T1 tumors, 15-LOX-1 was a positive activator of CREB. | [70] |
13-HPODE 13-HODE | Bovine mammary endothelial cells (BMEC), bovine monocytes | Streptococcus uberis | • 15-LOX-1 metabolite levels remained unchanged in BMEC exposed to Streptococcus uberis. • 13-HPODE and 13-HODE produced in bovine monocytes exposed to Streptococcus uberis. • BMEC treatment with 13-HPODE reduced endothelial barrier integrity, accelerate apoptosis while the effects reversed in co-treatment with antioxidant. | [71] |
15-LOX-1 | MCF-7 | purine-pyrazole hybrids | • 15-LOX-1 suppression using purine-pyrazole hybrids reduced the rate of viable MCF-7 cells | [34] |
15-HETE | TMT-081 rat mammary tumor cell line | Exogenous arachidonic acid/ to 15-HETE | • 15-HETE stimulate DNA synthesis in TMT-081 cells. • LOX inhibition using NDGA and esculetin resulted in TMT-081 cell growth suppression. • Exogenous arachidonic acid induced production of eicosanoids metabolites in TMT-081. | [74] |
13-HODE LOX | BT-20 cells | TGF alpha A23187 | • TGF alpha and A23187 caused 13-HODE formation in BT-20 cells. • LOX activity suppression reduced 13-HODE formation and DNA synthesis. • LOX activity and 13-HODE production are involved in transferring the mitogenic signals in breast cancer cell. | [75] |