Omega-6 Polyunsaturated Fatty Acids Enhance Tumor Aggressiveness in Experimental Lung Cancer Model: Important Role of Oxylipins

Abstract

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.

Association of Serum Unsaturated Fatty Acid Patterns with the Risk of Diabetic Nephropathy

“…Additionally, as a single-center retrospective analytical study, conducting a prospective multicenter study would enhance our comprehensive understanding of the association between FAPs and the risk of DN. Despite these limitations, our findings align with previous research and suggest potential intervention measures for preventing DN [14, 30‒33].…”

Effects of Crocodile Oil (Crocodylus siamensis) on Liver Enzymes: Cytochrome P450 and Glutathione S-Transferase Activities in High-fat DietFed Rats

“…Interestingly, the oil yields from this study presented ALA (0.96%) at similar levels compared with fish oil (1.45%) which is considered an omega-3-rich oil [ 45 , 46 ]. Furthermore, it was demonstrated that administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which is an obesogenic-related ligand of the AHR, in omega-3 fatty acids-fed mice reduced the growth rates of lung carcinoma-derived tumors and inhibited their metastasis to lung and liver [ 47 , 48 ]. This could suggest that omega-3 fatty acids could attenuate AHR activation and lead to other beneficial health effects.…”

Cellular Senescence, a Novel Area of Investigation for Metastatic Diseases

“…In cancer, PUFA are known to induce proliferation, apoptosis and angiogenesis [ 150 ]. However, their role in metastasis is still in its infancy due to the lack of experimental models which adequately recapitulate the complexity of human cancer, but recently, the intake of ω-6 PUFAs in the diet was shown to enhance the malignancy of tumor cells by the upregulation of pro-tumoral oxylipins (PGs, HETEs, DiHETrEs and HODEs) in a murine model of pulmonary squamous cell carcinoma, increasing proliferation, angiogenesis and molecular aggressiveness [ 151 ]. Increased oxylipin metabolism was also proposed as a marker for the evaluation of early stage of breast cancer [ 152 ].…”