Omega-6 Polyunsaturated Fatty Acids Enhance Tumor Aggressiveness in Experimental Lung Cancer Model: Important Role of Oxylipins.
Mayra Montecillo-AguadoBelen Tirado-RodriguezGabriela Antonio-AndresMario Morales-MartinezZhen TongJun YangBruce D HammockRogelio Hernandez-PandoSara Huerta-YepezPublished in: International journal of molecular sciences (2022)
Lung cancer is currently the leading cause of cancer death worldwide; it is often diagnosed at an advanced stage and bears poor prognosis. It has been shown that diet is an important environmental factor that contributes to the risk and mortality of several types of cancers. Intake of ω-3 and ω-6 PUFAs plays an important role in cancer risk and progression. Current Western populations have high consumption of ω-6 PUFAs with a ratio of ω-6/ω-3 PUFAs at 15:1 to 16.7:1 This high consumption of ω-6 PUFAs is related to increased cancer risk and progression. However, whether a diet rich in ω-6 PUFAs can contribute to tumor aggressiveness has not been well investigated. We used a murine model of pulmonary squamous cell carcinoma to study the aggressiveness of tumors in mice fed with a diet rich in ω-6 PUFAs and its relationship with oxylipins. Our results shown that the mice fed a diet rich in ω-6 showed a marked increase in proliferation, angiogenesis and pro-inflammatory markers and decreased expression of pro-apoptotic proteins in their tumors. Oxylipin profiling revealed an upregulation of various pro-tumoral oxylipins including PGs, HETEs, DiHETrEs and HODEs. These results demonstrate for the first time that high intake of ω-6 PUFAs in the diet enhances the malignancy of tumor cells by histological changes on tumor dedifferentiation and increases cell proliferation, angiogenesis, pro-inflammatory oxylipins and molecular aggressiveness targets such as NF-κB p65, YY1, COX-2 and TGF-β.
Keyphrases
- poor prognosis
- physical activity
- weight loss
- long non coding rna
- squamous cell carcinoma
- cell proliferation
- signaling pathway
- anti inflammatory
- endothelial cells
- cell death
- vascular endothelial growth factor
- single cell
- type diabetes
- high fat diet induced
- weight gain
- metabolic syndrome
- cardiovascular disease
- body mass index
- toll like receptor
- cardiovascular events
- oxidative stress
- lps induced
- insulin resistance
- human health
- young adults
- binding protein
- squamous cell