Endogenously synthesized n-3 fatty acids in fat-1 transgenic mice prevent melanoma progression by increasing E-cadherin expression and inhibiting β-catenin signaling

Abstract

Malignant melanoma is the most lethal form of skin cancer. Although preclinical studies have shown that n-3 polyunsaturated fatty acids (PUFAs) are beneficial for prevention of melanoma, the molecular mechanisms underlying the protective effects of n‑3 PUFAs on melanoma remain largely unknown. In the present study, endogenously increased levels of n-3 PUFAs in the tumor tissues of omega‑3 fatty acid desaturase (fat‑1) transgenic mice was associated with a reduction in the growth rate of melanoma xenografts. This reduction in tumor growth in fat‑1 mice compared with wild‑type controls may have been associated, in part, to the: i) Increased expression of E‑cadherin and the reduced expression of its transcriptional repressors, the zinc finger E‑box binding homeobox 1 and snail family transcriptional repressor 1; ii) significant repression of the epidermal growth factor receptor/Akt/β‑catenin signaling pathway; and iii) formation of significant levels of n‑3 PUFA‑derived lipid mediators, particularly resolvin D2 and E1, maresin 1 and 15‑hydroxyeicosapentaenoic acid. In addition, vitamin E administration counteracted n‑3 PUFA‑induced lipid peroxidation and enhanced the antitumor effect of n‑3 PUFAs, which suggests that the protective role of n‑3 PUFAs against melanoma is not mediated by n‑3 PUFAs‑induced lipid peroxidation. These results highlight a potential role of n‑3 PUFAs supplementation for the chemoprevention of melanoma in high‑risk individuals, and as a putative adjuvant agent in the treatment of malignant melanoma.

Metabolic reprogramming in cancer cells, consequences on pH and tumour progression: Integrated therapeutic perspectives with dietary lipids as adjuvant to anticancer treatment

“…Similarly, it was found that increasing the endogenous levels of n-3 PUFA, using n-3 fatty acid desaturase (fat-1) transgenic mice, was associated with a reduction in the growth rate of melanoma xenografts. This reduction in melanoma growth in fat-1 mice, compared with wild-type mice, was associated with an increased expression of E-cadherin and the reduced expression of its transcriptional repressors, Zeb-1 and Snail-1 (293). It also significantly repressed the EGFR/Akt/β-catenin signalling pathway and induced the formation of significant levels of anti-inflammatory n-3 PUFA-derived lipid mediators, such as resolvin D2 and E1, maresin 1 and 15-hydroxyeicosapentaenoic acid (293).…”

Pharmacological and nutritional targeting of voltage-gated sodium channels in the treatment of cancers

“…Autophagy inhibition suppressed apoptosis, and autophagy induction further enhanced apoptosis in response to DHA treatment (Jing et al, 2011). There is evidence that n-3 PUFA may inhibit the expression of EMT markers and reduce associated invasive properties in cancer cells (D'eliseo et al, 2016;Yin et al, 2016). Altogether, these effects could bring beneficial values to delay the appearance/diagnosis of a primary tumor and as such be of interest in primary prevention.…”

Effects of ω-3 fatty acids and ratio of ω-3/ω-6 for health promotion and disease prevention

“…Dr. Jing X. Kang, who is director of the Harvard Center for Fatty Acid Research, noted that fatty acids, as well as vitamins and amino acids, are one of the most important nutrients in the human body. PUFAs ω-3 are one of two essential fatty acids that the human body cannot synthesize and that must enter the body with food, and the other -ω-6 fatty acids (Meester & Watson, 2008;Delpech et al, 2015;Liu et al, 2014;Luo et al, 2021;Wu et al, 2016;Yin et al, 2016).…”