Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors

Abstract

Dietary fish oils have potential for prevention of colon cancer, and yet the mechanisms of action in normal and tumor colon tissues are not well defined. Here we evaluated the impact of the colonic fatty acid milieu on formation of prostaglandins and other eicosanoids. Distal tumors in rats were chemically induced to model inflammatory colonic carcinogenesis. After 21 weeks of feeding with either a fish oil diet containing an eicosapentaenoic acid:ω-6 fatty acid ratio of 0.4 or a Western fat diet, the relationships between colon fatty acids and prostaglandin E2 (PGE2) concentrations were evaluated. PGE2 is a key pro-inflammatory mediator in the colon tightly linked with the initiation and progression of colon cancer. The fish oil versus the Western fat diet resulted in reduced total fatty acid concentrations in serum but not in colon. In the colon, the effects of the fish oil on fatty acids differed in normal and tumor tissue. There were distinct lipodomic patterns consistent with a lipogenic phenotype in tumors. In tumor tissue, the eicosapentaenoic acid:arachidonic acid ratio, cyclooxygenase-2 expression and the mole percent of saturated fatty acids were significant predictors of inter-animal variability in colon PGE2 after accounting for diet. In normal tissues from either control rats or carcinogen-treated rats, only diet was a significant predictor of colon PGE2. These results show that the fatty acid milieu can modulate the efficacy of dietary fish oils for colon cancer prevention, and this could extend to other preventive agents that function by reducing inflammatory stress.

Mass spectrometry‐based lipidomics in food science and nutritional health: A comprehensive review

“…For PC, the increase of PC(18:2/20:2), PC(20:2/18:2), PC(18:3/18:2), PC(18:2/18:3), PC(18:2/18:2), and PC(16:2/18:2) and the decrease of PC(20:1/18:1) and PC(16:1/16:1) were determined (Sundaram et al., 2018). Similarly, changes in fatty acids level have been shown to be a key event in colorectal cancer (Djuric et al., 2017). Changes in colonic lipids were quantified by comparing the consumption of fish oil with western mixed fats.…”

“…Nutrition/diet is a potentially modifiable cancer risk factor, and a healthy diet is associated with a lower incidence and prevalence of cancer, especially gastrointestinal cancers, such as colon cancer (Notarnicola et al., 2018). Dietary fish oil is considered to have potential to prevent colon cancer (Djuric et al., 2017). Adherence to a Mediterranean diet was reported to reduce the risk of breast, lung (Krusinska et al., 2018), and prostate cancer (Urquiza‐salvat et al., 2019).…”

Fatty acid and lipidomic data in normal and tumor colon tissues of rats fed diets with and without fish oil

“…The related research article [1] does not report all the fatty acids singly. In addition, a subset of the tissue samples was analyzed by lipidomics and the heat maps of all the lipids that were identified by hierarchical cluster analyses to differ by tissue type or diet type are shown in Fig.…”

“…There were 10 rats per group. ANOVA of fatty acid classes is shown in the accompany research paper [1].Fatty acid (mole % or mole ratio)Serum of control ratsSerum of carcinogen-treated ratsWestern fat dietFish oil dietWestern fat dietFish oil diet12:02.62 (0.25)3.23 (0.79)3.19 (0.87)3.37 (0.65)14:02.64 (0.25)2.98 (0.52)2.94 (0.45)2.96 (0.36)16:027.12 (1.62)26.72 (1.95)25.75 (1.58)25.74 (1.79)16:12.08 (0.41)2.59 (0.34)1.54 (0.55)2.07 (0.41)18:010.78 (1.05)10.86 (1.00)11.03 (0.94)12.04 (0.77)18:123.88 (1.37)15.71 (1.53)*23.39 (1.51)14.47 (1.02)*18:2, ω-611.58 (0.58)10.45 (0.83)12.46 (1.39)11.03 (0.33)18:3, ω-30.31 (0.03)0.52 (0.06)*0.34 (0.06)0.47 (0.04)*20:10.31 (0.02)0.19 (0.04)*0.31 (0.02)0.19 (0.03)*20:3, ω-3-60.57 (0.05)0.81 (0.12)*0.51 (0.06)0.88 (0.06)*20:4, ω-614.12 (1.65)7.37 (1.39)*14.55 (1.90)7.96 (0.82)*20:5, ω-30.23 (0.05)7.00 (0.70)*0.22 (0.06)6.85 (0.83)*22:4, ω-61.09 (0.19)0.40 (0.11)*1.09 (0.19)0.40 (0.11)*22:5, ω-30.71 (0.11)3.34 (0.53)*0.71 (0.12)3.34 (0.53)*22:6, ω-31.95 (0.34)7.84 (1.49)*2.02 (0.29)8.19 (0.96)*Ratio 18:1–18:02.24 (0.32)1.47 (0.24)*2.14 (0.29)1.21 (0.15)*Ratio 16:1–16:00.08 (0.01)0.10 (0.01)*0.06 (0.02)0.08 (0.01)…”

“…There were 10 rats per group and 9 per group for tumor tissue from carcinogen-treated rats fed the fish oil diet. ANOVA of fatty acid classes is shown in the accompany research paper [1].Fatty acid (mole %, or mole ratio)Normal tissue from control ratsNormal tissue from carcinogen-treated ratsTumor tissue from carcinogen-treated ratsWestern fat dietFish oil dietWestern fat dietFish oil dietWestern fat dietFish oil diet12:05.47 (1.85)4.73 (0.78)6.73 (1.42)5.82 (1.19)4.06 (1.78)6.14 (2.51)14:04.69 (0.68)4.84 (1.26)4.83 (0.82)4.91 (0.62)3.72 (0.91)3.91 (1.23)16:019.11 (1.61)19.00 (2.51)18.95 (1.40)20.26 (2.15)21.11 (1.23)20.88 (2.49)16:15.74 (1.68)9.78 (1.68)*4.91 (1.85)8.99 (3.02)2.90 (1.02)4.32 (1.50)18:06.90 (3.41)5.76 (2.20)5.16 (2.13)6.60 (2.94)11.46 (2.10)9.75 (3.24)18:133.52 (6.90)29.28 (2.93)*36.95 (5.43)27.00 (4.45)*24.1 (3.71)21.6 (5.6)18:2, ω-613.31 (1.62)13.44 (0.72)14.09 (0.94)12.60 (0.96)11.1 (0.96)12.2 (1.00)18:3, ω-30.52 (0.13)0.80 (0.12)*0.51 (0.16)0.73 (0.15)0.33 (0.19)0.68 (0.20)*20:10.44 (0.24)0.36 (0.21)0.32 (0.19)0.37 (0.15)1.78 (0.63)0.66 (0.30)20:3, ω-3-60.62 (0.34)0.70 (0.33)0.56 (0.31)0.76 (0.33)0.62 (0.28)1.75 (0.50)20:4, ω-6 (AA)5.98 (3.61)4.16 (2.08)3.82 (2.26)4.14 (1.79)12.6 (3.7)7.18 (3.23)20:5, ω-3 (EPA)1.45 (0.80)2.61 (1.03)1.34 (1.31)3.31 (1.65)2.12 (1.48)5.19 (2.74)22:4 ω-6 (DTA)0.93 (0.52)0.41 (0.25)0.66 (0.37)0.38 (0.16)1.78 (0.63)0.66 (0.30)*22:5, ω-3 (DPA)…”