脂氧酶调节对大鼠肝癌前病变的影响

目的 观察脂氧酶调节的抑制剂-槲皮素（QU）在肝癌发生过程，即癌前病灶转化为增生结节过程中的作用，探讨脂氧酶调节对肝癌发生的影响。方法利用大白鼠复制肝癌前病变发生的动物模型，然后将带有癌前病灶的大鼠分组。实验组分别给予0．75％，1．5％槲皮素，加或不加0．05％苯巴比妥（PB）的饲料，对照组只给予单纯0．05％PB饲料或基础饲料喂养9周。处死取肝后，进行r-谷胺酰转换酶（GGT）组化染色和HE染色。结果0．75％。1．5％槲皮素，加或不加PB的实验组中，单位面积的GGT染色阳性的持续性结节数和HE染色的肝细胞增生性结节数与相应对照组相比显著减少（P〈0．05）。结论2种浓度的槲皮素在有或没有PB-癌促进剂作用下，均对肝癌前病灶转化增生结节的过程有抑制作用，提示脂氧酶调节通路与肝癌的发生有关。     

Conjugated linoleic acid alters caveolae phospholipid fatty acid composition and decreases caveolin-1 expression in MCF-7 breast cancer cells

Conjugated linoleic acid (CLA) refers to a group of biologically active fatty acids that exhibit anticarcinogenic properties; however, the mechanism of action remains poorly understood. Caveolae are specialized plasma membrane structures that affect many facets of cancer cell function, including growth, cell signaling, and apoptosis. Therefore, one potential mechanism could be alteration of caveolae lipid composition and function. We hypothesized that CLA can alter the lipid microenvironment of caveolae and alter expression of the major caveolae-resident protein, caveolin-1. MCF-7 human breast cancer cells were treated with a vehicle control, linoleic acid (LA), or CLA for 3 days after which total cell lysate, plasma membrane, and caveolae membrane fractions were isolated. Our findings indicate that CLA readily incorporates into caveolae (Δ9cis,11trans-18:2 being the major isomer) and maybe preferentially enriched in specific phospholipid species. Furthermore, caveolin-1 localization to caveolae after treatment with CLA was decreased relative to either control- or LA-treated cells, without changes in total cellular levels of protein relative to vehicle-control treated cells. Taken together, our results suggest that further investigation of a potential therapeutic role for CLA in modulating caveolae function in breast cancer is merited.     

Erythrocyte membrane microviscosity and phospholipid composition in lead workers

The microviscosity and fluidity of erythrocyte ghost membranes from lead workers and control subjects was measured by fluorescence polarisation using the fluorophore, 1,6-diphenyl-1,3,5-hexatriene (DPH). Increased lead was associated with a significant decrease in the average microviscosity of resealed and unsealed erythrocyte membranes. Since DPH fluorescence reflects the organisation of lipids in the central core of the membrane, two aspects of phospholipid metabolism were investigated. Phospholipids were extracted from red blood cell ghost membranes and identified by high performance liquid chromatography. The ratio of phosphatidyl choline to phosphatidyl ethanolamine, an established correlate of membrane fluidity, was significantly increased in lead workers. This is attributed to the known increases in red blood cell cholesterol in lead workers and the structural incompatibility of phosphatidyl ethanolamine and cholesterol, which result in a compensatory increase of phosphatidyl choline. Erythrocyte ghost membranes from control subjects were resealed with the intermediates in phospholipid synthesis that increase with a lead inhibited decrease in red blood cell pyrimidine 5'-nucleotidase. Membrane fluidity was not modified by incubation with cytidine triphosphate, uridine triphosphate, cytidine diphosphate choline, or cytidine diphosphate ethanolamine. Alterations in the microviscosity of the lipid regions of the hydrophobic core of the erythrocyte membrane bilayer and in the phospholipid composition of the membrane may be defects which contribute to the clinical and biochemical instability of the red blood cell on exposure to lead.     

磷脂酶A2调节对大鼠肝癌前病变作用

目的 观察磷脂酶A2调节的鼠肝癌发生过程，即癌前病灶转化为增生结节过程中的作用，探讨磷脂酶A2对肝癌发生影响。方法 利用大白鼠复制肝癌前病变发生的动物模型。然后将带有癌前病灶的大鼠分组。实验组分别给0．75％，1，5％p-bromophenacylbromie（BPB），加有或不加0．05％苯巴比妥（PB）的饲料，对照组只给单纯0．05％PB饲料或基础饲料喂养9周。处死取肝后，进行r-各胺酰转换酶（GGT）组化染色和HE染色。结果0．75％．1．5％BPB、加有或不加PB的实验组中，单位面积的GGT染色阳性的持续性结节数和HE染色的肝细胞增生性结节数与相应对照组相比显著减少（P〈0．05）。结论 2种浓度的BPB在有或没有PB-癌促进剂作用下，均在肝癌前病灶转化为增生结节的过程有抑制作用，提示磷脂酶A2参与肝癌的发生过程。     

Erythrocyte membrane microviscosity and phospholipid composition in lead workers.

The microviscosity and fluidity of erythrocyte ghost membranes from lead workers and control subjects was measured by fluorescence polarisation using the fluorophore, 1,6-diphenyl-1,3,5-hexatriene (DPH). Increased lead was associated with a significant decrease in the average microviscosity of resealed and unsealed erythrocyte membranes. Since DPH fluorescence reflects the organisation of lipids in the central core of the membrane, two aspects of phospholipid metabolism were investigated. Phospholipids were extracted from red blood cell ghost membranes and identified by high performance liquid chromatography. The ratio of phosphatidyl choline to phosphatidyl ethanolamine, an established correlate of membrane fluidity, was significantly increased in lead workers. This is attributed to the known increases in red blood cell cholesterol in lead workers and the structural incompatibility of phosphatidyl ethanolamine and cholesterol, which result in a compensatory increase of phosphatidyl choline. Erythrocyte ghost membranes from control subjects were resealed with the intermediates in phospholipid synthesis that increase with a lead inhibited decrease in red blood cell pyrimidine 5'-nucleotidase. Membrane fluidity was not modified by incubation with cytidine triphosphate, uridine triphosphate, cytidine diphosphate choline, or cytidine diphosphate ethanolamine. Alterations in the microviscosity of the lipid regions of the hydrophobic core of the erythrocyte membrane bilayer and in the phospholipid composition of the membrane may be defects which contribute to the clinical and biochemical instability of the red blood cell on exposure to lead.     

The effects of dietary fat and selenium on the development of preneoplastic lesions in rat liver

In this study, the effects of dietary fat and selenium on the development of putative preneoplastic foci induced by aflatoxin B1 were examined. Rat hepatic gamma-glutamyl transpeptidase (GGT) activity, selenium-dependent glutathione peroxidase activity, glutathione, and total lipid were analyzed 3 and 13 weeks after the start of dietary and carcinogen treatment. Results indicate that high dietary fat has an enhancing effect on the development of preneoplastic foci. A high-fat, selenium-deficient diet resulted in an increase in foci development, but the increase was not significant. An interaction between aflatoxin and the two nutrients was also observed in liver glutathione content and GGT activity at Week 3.     

Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brain

The importance of maternal dietary fatty acids on arachidonic acid [AA; 20:4(n-6)] and docosahexaenoic acid [DHA; 22:6(n-3)] in fetal brain nerve growth cone membranes and monoaminergic neurotransmitters was investigated. Rats were fed purified diets containing 20 g/100 g safflower oil with 74.3% 18:2(n-6), 0.2% 18:3(n-3), soybean oil with 55.4% 18:2(n-6), 7.7% 18:3(n-3) or high fish oil with 24.6% 22:6(n-3) through gestation. Tissue for rats within a litter were pooled at birth, brain growth cone membranes prepared and phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) fatty acids quantified by gas-liquid chromatography. Dopamine, serotonin, and the metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxyindolacetic acid were quantified by HPLC. Growth cone membranes from offspring of rats fed safflower oil had significantly lower, and offspring of rats fed high 22:6(n-3) fish oil had significantly higher 22:6(n-3) in PE, PS and PI than the soybean oil group. The growth cone membrane PC, PE and PS 20:4(n-6) was significantly lower in the fish oil than in the soybean or safflower oil groups. Serotonin concentration was significantly higher in brain of offspring in the safflower oil compared with the soybean oil group. The newborn brain dopamine was inversely related to PE DHA and PS DHA (P < 0.001), but positively related to PC AA (P < 0.05). These studies show that maternal dietary fatty acids may alter fetal brain growth cone (n-6) and (n-3) fatty acids, and neurotransmitters involved in neurite extension, target finding and synaptogenesis. The functional importance, however, is not known at this time.     

Diet (n-3) polyunsaturated fatty acid content and parity affect liver and erythrocyte phospholipid fatty acid composition in female rats

The fatty acid composition of membrane phospholipids affects the physicochemical properties of the membrane and thus influences cell function. In this study, the effects of 1-4 sequential pregnancies on the phospholipid fatty acid compositions of the maternal liver and erythrocytes were determined in female rats fed diets containing alpha-linolenic acid (ALA), ALA and preformed docosahexaenoic acid (DHA; ALA+DHA), or minimal ALA (low ALA). Virgin females, fed the diets for commensurate durations, served as a control for reproduction. Liver and erythrocyte total phospholipid compositions were determined at weaning by TLC/GC. In both tissues, significant main effects of diet and reproductive status were detected for many fatty acids, but a significant interaction of diet, reproductive status, and duration of treatment (no. of reproductive cycles or equivalent time period for virgins) was detected only for DHA, 22:6(n-3). Primiparous dams fed the ALA and low ALA diet had decreased liver DHA content of 31% and 74%, respectively, compared with virgin females fed the ALA diet. Liver DHA did not decrease further after additional reproductive cycles. Liver DHA content was unchanged in parous dams fed the ALA+DHA diet, but virgin females fed this diet exhibited a 50% increase in liver DHA after 13 wk of treatment. Changes in erythrocyte DHA were of similar magnitude and time course to those observed in liver, suggesting that this tissue may serve as a marker for liver DHA status.     

Long-chain fatty acid composition of maternal liver lipids during pregnancy and lactation in the rat: comparison of triglyceride to phospholipid

The change in long-chain fatty acid composition in maternal liver was studied during pregnancy and lactation in the rat. Maternal liver triglycerides and phospholipids transiently accumulated and were depleted of long-chain fatty acids during pregnancy and lactation. During pregnancy, maternal liver accumulated triglyceride, but triglyceride fatty acid composition changed little. However, maternal liver total phospholipid fatty acid composition changed significantly without a change in the total pool size throughout pregnancy or lactation. The change in composition of (n-3) and (n-6) essential fatty acids in maternal liver triglyceride and total phospholipid occurred in an apparently dyssynchronous manner throughout pregnancy and lactation.     

花生油、茶油、牛油对大鼠脂质过氧化、膜磷脂脂肪酸组成及膜流动性的影响

用含11％花生油、茶油、牛油的饲料分别饲养SD大鼠，观察其血清和心、肝、脑丙二醛（MDA）、血清和肝超氧化物歧化酶（SOD）水平、生物膜磷脂脂肪酸组成及膜流动性的改变。结果发现：花生油组心线粒体及牛油组RBC膜磷脂脂肪酸含量与摄入脂肪酸呈正相关（r分别为0.6275和0.6967，P＜0.01）。喂饲花生油引起生物膜磷脂多不饱和脂肪酸含量增加，膜流动性增高，血清和肝SOD水平较低（分别为3.76±1.61mg／L、616±163μg／g），血清MDA较高（8.70±1.71μmol／L），提示脂质过氧化程度较高。喂饲茶油引起膜磷脂单不饱和脂肪酸含量增加，膜流动性和血清SOD（5.66±2.00mg／L）较高，血清及脑MDA较低（5.92±1.15μmol／L，2.45±0.44μmol／g），提示脂质过氧化程度较低。喂饲牛油引起膜磷脂饱和脂肪酸含量增加，膜流动性较低，血清及肝SOD较高（5.79±0.56mg／L，886±99μg／g），血清MDA较低（7.04±1.66μmol／L），脑MDA较高（3.96±1.68μmol／g），脂质过氧化程度介于花生油组与茶油组之间。     

The effect of dietary essential fatty acid deficiency on the composition and properties of the liver microsomal membrane of rats

The effect of dietary essential fatty acid (EFA) deficiency on lipid composition, fluidity and important enzyme and transport activities of liver microsomal membrane was studied in weanling rats. After 133 d of EFA deficiency, no difference was noticed in membrane phospholipid, cholesterol and protein levels, but a significant change occurred in the fatty acid composition of bilayer phospholipids. In EFA-deficient rats, linoleic (18:2(n-6] and arachidonic (20:4(n-6] acids were both severely lower while oleic (18:1(n-9], palmitoleic (16:1(n-7] and particularly 5,8,11-eicosatrienoic (20:3(n-9] acids were significantly higher than in controls. The higher level of the latter tended to compensate for the lower level of 20:4(n-6). Membrane fluidity, as estimated by the reciprocal of the order parameter S, was lower in the deficient rats than in the controls, and all the measured microsomal enzyme activities were markedly affected. NADH-Cyt b5 electron transferring system, coupled with the fatty acid desaturation system, was higher than in controls. In contrast, the cytochrome P450 complex activity was lower and some of the important liver detoxifying enzyme activities were lower due to physical-chemical changes in the microsomal membrane. Calcium uptake and Ca2+-ATPase activity were also significantly lower in EFA-deficient rats than in controls. It was concluded that fatty acid composition may be the major factor contributing to membrane fluidity and function and that EFA might play a role in regulating the intrinsic membrane protein activities.     

Effects of different quantities of fat on serum and liver lipids, phospholipid class distribution and fatty acid composition in alcohol-treated rats

The present study investigated the quantitative effect of dietary fats and ingestion of alcohol on serum and liver lipids, fatty acid bound to phospholipids and their class distribution of male Wistar rats. The rats in C (control) and A (alcohol) groups were fed a standard laboratory diet, HFC (high fat-control) and HFA (high fat-alcohol) groups were fed a high fat diet (standard diet supplemented with 20 g%w/w, sunflower oil: lard mixture 1: 1) for 6 wk. Alcohol-treated rats consumed alcohol at the rate of 9 g/kgbw/d (15-20% energy). Liver phospholipid (PL) content was decreased, and phospholipid/cholesterol liver molar ratio increased in the alcohol treated rats. The proportion of serum sphingophospholipid (Sph) was significantly lower and proportion of phosphatidylcholin (PC) significantly higher in serum PL in alcohol-treated rats. Phospholipid class distribution was unaffected by alcohol feeding in liver. Significantly lower levels of 16:1n-7 and higher levels of 20:5n-3 and 22:4n-6 in the serum PL were observed in the alcohol-treated rats. The groups on the HF diet increased levels of 20:4n-6, 22:4n-6 and total n-6, polyunsaturated fatty acid (PUFA) and decreased levels of 18:1n-9 and total monounsaturated fatty acids (MUFA)in both liver and serum PL, but n-3 fatty acid increased in serum PL and decreased in liver PL compared to groups on the standard diet. Alcohol fat interaction was evident in MUFA and PUFA/SFA in serum PL and n-6, MUFA, PUFA and polyunsaturated/saturated fatty acid ratios (PUFA/SFA) in liver PL. This study showed that the high fat intake in alcohol-treated rats increased levels of 20:4n-6, 22:4n-6 and 20:4/18:2 ratio, and decreased level of 18:1n-9 in liver and serum phospholipids.     

Supplementation of omega-3 fatty acids in parenteral nutrition beneficially alters phospholipid fatty acid pattern

BACKGROUND: The clinical safety and the uptake of omega-3 polyunsaturated fatty acids (PUFA) into the serum phospholipids and erythrocyte membranes after administration of fish-oil-supplemented parenteral nutrition (PN) was investigated in colorectal surgical patients. METHODS: Forty patients undergoing colorectal surgery (n = 40) and with an indication for PN were enrolled in a prospective, double-blind, randomized study to receive an omega-3 PUFA-supplemented 20% lipid emulsion (Lipoplus; B. Braun Melsungen, Melsungen, Germany; test group, n = 19) for 5 days postoperatively. The control group received a standard 20% fat emulsion (Lipofundin MCT/LCT, B. Braun Melsungen, Melsungen, Germany, control group, n = 21). Clinical outcome parameters and safety were assessed by means of adverse events recording clinical parameters and hematologic analyses. The contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as arachidonic acid (AA), in phospholipid fractions in plasma and in erythrocytes were analyzed preoperatively, on postoperative days 1, 6, and 10 using liquid gas chromatography. RESULTS: Both fat emulsions were well tolerated, and none of the adverse events was considered to be related to treatment. Postoperative infectious complications occurred in 4 patients of the omega-3 PUFA group vs 7 patients in the control group. As compared with the control group, the omega-3 PUFA group had significantly increased levels of EPA in the membranes of the erythrocytes in postoperative day 6 (2.0% +/- 0.9% vs 0.8% +/- 0.5% fatty acid methyl esters, [FAME]) and postoperative day 10 (2.1% +/- 0.8% vs 0.9% +/- 0.7% FAME, p < .05). Also, the EPA levels in the serum phospholipids were significantly higher than in the control group on the same postoperative days (7.0% +/- 2.6% vs 1.3% +/- 0.8% and 3.6% +/- 1.0% vs 1.0% +/- 0.4% FAME, p < .05). The DHA levels in the serum phospholipids were significantly higher in the omega-3 PUFA group compared with the control on postoperative days 6 and 10 (11.8% +/- 1.9% vs 8.4% +/- 1.5% and 11.2% +/- 1.6% vs 8.5% +/- 1.4% FAME, p < .05). AA levels were not significantly different in the both groups. CONCLUSIONS: Omega-3-fatty-acids-supplemented fat emulsions for parenteral administration are safe and very well tolerated. This study demonstrates that parenteral administration of omega-3-PUFA-enriched fat emulsions leads to increased incorporation of EPA and DHA into phospholipids in serum and erythrocytes, whereas AA levels remain unchanged. Thus, postoperative parenteral administration of omega-3-PUFA-enriched lipid emulsions could have an impact on the postoperative inflammatory response after abdominal surgery and could be used in standard postoperative care when PN is indicated.     

Preoperative oral supplementation with long-chain Omega-3 fatty acids beneficially alters phospholipid fatty acid patterns in liver, gut mucosa, and tumor tissue

BACKGROUND: The uptake of omega-3 polyunsaturated fatty acids (PUFAs) into the liver, gut mucosa, and tumor tissue and plasma levels after preoperative administration of supplemented enteral nutrition was investigated in patients with malignancies of the upper gastrointestinal tract. The objective of the study was to evaluate the incorporation of preoperatively administrated PUFAs, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) into cell phospholipids. METHODS: Patients undergoing major gastrointestinal surgery (n = 40) were prospectively randomized to receive a PUFA-supplemented liquid oral diet 5 days preoperatively or an isocaloric control diet. The planned diet intake was 1000 mL/d providing 3.7 g of PUFA. The diet was given in addition to the usual hospital diet. The phospholipid fractions in plasma were analyzed on the day of surgery. Tissue samples of liver, gut mucosa (small intestine), and tumor were taken during surgery and homogenized. EPA and DHA content was analyzed using liquid gas chromatography. RESULTS: Both patient groups (PUFA group: n = 20; control group: n = 20) were similar in age, weight, and surgical procedures. As compared with the control group, the PUFA group had significantly increased levels of EPA in liver tissue (0.4 vs 1.3 weight %), gut mucosa (0.3 vs 1.0 weight %), and tumor tissue (0.3 vs 0.8 weight %). Also, the DHA levels in the PUFA group were significantly higher than the control group: liver tissue (4.1 vs 7.5 weight %), gut mucosa (2.1 vs 3.7 weight %) and tumor tissue (1.9 vs 4.2 weight %). CONCLUSIONS: This study suggests that administration of PUFA-enriched diets leads to increased incorporation of EPA and DHA not only in liver and gut mucosa tissue, but also in tumor tissue in patients with solid gastrointestinal tumors. Thus, preoperative administration of oral PUFA-enriched diets could have an impact on the postoperative inflammatory response after major abdominal surgery.     

Rates of H2O2 generation from peroxisomal beta-oxidation are sufficient to account for fatty acid-stimulated ethanol metabolism in perfused rat liver

Fatty acids generate H2O2 via peroxisomal beta-oxidation and increase ethanol metabolism markedly in a system that involves catalase-H2O2. The present studies were conducted to understand why fatty acid-stimulated ethanol metabolism occurs much faster than rates of H2O2 generation reported previously in perfused rat liver. A new method was developed to measure rates of H2O2 generation based on the fact that methanol is oxidized only by catalase in rat liver. Rates of H2O2 generation were estimated from the time necessary for the steady-state level of catalase-H2O2 measured spectrophotometrically (660-640 nm) through a lobe of the liver to return to basal values following the addition of a known quantity of methanol in a closed perfusion system containing 4% bovine serum albumin. Under these conditions, basal rates of H2O2 production and rates of 4-methylpyrazole-insensitive ethanol oxidation were in a similar range (10 to 20 mumol/g/hr). Rates of H2O2 generation were increased up to 80 mumol/g/hr by addition of laurate, palmitate or oleate (1 mM); half-maximal increases in rates were observed with 0.6 mM oleate. Hexanoate, a short-chain fatty acid, did not stimulate H2O2 production or ethanol uptake. In these studies, rates of H2O2 generation compared well with rates of fatty acid-stimulated ethanol uptake measured in the presence of 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, with all fatty acids studied. It is concluded, therefore, that rates of H2O2 generation are sufficient to account for rates of fatty acid-stimulated ethanol metabolism via catalase-H2O2. In addition, these data indicate that catalase may contribute significantly to ethanol oxidation under physiological conditions in the presence of fatty acids.     

共轭亚油酸对人乳腺癌细胞生长的抑制作用

目的 研究共轭亚油酸（c9,t11-CLA)对人乳腺癌细胞（MCF－7）生长的影响。方法 采用细胞核分裂指数、细胞生长曲线、细胞集落形成试验、^3H-TdR掺入试验和软琼脂培养方法,所设剂量（μmol/L）为25,50,100,200,以96％乙醇为溶剂对照。结果 在细胞核分裂指数、细胞生长曲线和细胞集落形成试验中,可见c9,t11-CLA对MCF－7细胞生长有明显的抑制作用,其作用于MCF－7细胞8d后的抑制率（％）分别为27．18、35．43、91．05和92．86;在^3H-TdR掺入试验中,可见随着c9,t11-CLA剂量的增加,^3H-TdR掺入到MCF－7细胞中明显的减少,与阴性对照组相比差异有显性;由软琼脂培养试验结果可见,随着c9,t11-CLA剂量的增加,MCF－7细胞的集落形成逐渐降低,除了25 μmol/L剂量组外与阴性对照组相比差异有显性。结论 c9,t11-CLA对MCF－7细胞的生长有明显的抑制作用。     

Conjugated eicosapentaenoic acid (EPA) inhibits transplanted tumor growth via membrane lipid peroxidation in nude mice

Both conjugated linoleic acid (CLA) and eicosapentaenoic acid (EPA) have an antitumor effect. Hence, we hypothesized that a combination of conjugated double bonds and an (n-3) highly unsaturated fatty acid would produce stronger bioactivity. To verify the antitumor effect of conjugated EPA (CEPA), we transplanted DLD-1 human colon tumor cells into nude mice, and compared the tumor growth between CEPA-fed mice and CLA- and EPA-fed mice. After tumor cell inoculation, mice were assigned to 1 of 4 groups (control, CLA, EPA, and CEPA) consisting of 10 mice each. The control group received only safflower oil fatty acids, whereas the remaining groups received a mixture of safflower oil fatty acids and 20 g/100 g of total fatty acids as CLA, EPA, or CEPA. Mice were fed once every 2 d for 4 wk at a dose of 50 mg/mouse at each feeding. After 4 wk, tumor growth in CEPA-fed mice was significantly suppressed, compared with that in CLA- (P < 0.005) and EPA-fed mice (P < 0.001). DNA fragmentation in the tumor tissues of the CEPA-fed mice occurred more frequently than in the CLA- (P < 0.001) and EPA-fed mice (P < 0.001), suggesting that CEPA induced apoptosis in the tumor tissues. To further investigate the mechanism, the level of oxidative stress in the tumor tissues was determined. The CEPA-fed mice showed significant lipid peroxidation, compared with the CLA- (P < 0.001) and EPA-fed mice (P < 0.001). Therefore, we verified that CEPA has a stronger in vivo antitumor effect than EPA and CLA, and that CEPA acts through induction of apoptosis via lipid peroxidation.