• Journal of Cancer Prevention
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• v.22 no.1
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• pp.1-5
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• 2017

Pancreatic cancer is a highly aggressive malignant tumor of the digestive system and radical resection, which is available to very few patients, might be the only possibility for cure. Since therapeutic choices are limited at the advanced stage, prevention is more important for reducing incidence in high-risk individuals with family history of pancreatic cancer. Epidemiological studies have shown that a high consumption of fish oil or ${\omega}3-polyunsaturated$ fatty acids reduces the risk of pancreatic cancers. Dietary fish oil supplementation has shown to suppress pancreatic cancer development in animal models. Previous experimental studies revealed that several hallmarks of cancer involved in the pathogenesis of pancreatic cancer, such as the resistance to apoptosis, hyper-proliferation with abnormal $Wnt/{\beta}-catenin$ signaling, expression of pro-angiogenic growth factors, and invasion. Docosahexaenoic acid (DHA) is a ${\omega}3-polyunsaturated$ fatty acid and rich in cold oceanic fish oil. DHA shows anti-cancer activity by inducing oxidative stress and apoptosis, inhibiting $Wnt/{\beta}-catenin$ signaling, and decreasing extracellular matrix degradation and expression of pro-angiogenic factors in pancreatic cancer cells. This review will summarize anti-cancer mechanism of DHA in pancreatic carcinogenesis based on the recent studies.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.1
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• pp.31-38
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• 2014

Docosahexaenoic acid (DHA, 22:6n-3) and ecosapentaenoic acid (20:5n-3) have attracted increasing attention since the first epidemiological report on the importance of n-3 essential fatty acids. It is thought that DHA has important functions in brain and retinal tissues. Thraustochytrids, a group of marine protists, are capable of heterotrophic growth, and are potential omega-3 producers for industrial use, especially the members of the Schizochytrium and Thraustochytrium genera. The aims of this work were to isolate, identify and screen thraustochytrids from 17 different locations. Twenty-three isolates were screened for biomass, total fatty acid (TFA) and DHA content. Analysis of the fatty acid methyl esters revealed four distinct clusters biomass ranged from $8.68-9.36gL^{-1}$, and lipid and DHA contents ranged from $3.11-4.10gL^{-1}$ and $1.05-1.93gL^{-1}$ biomass, respectively. B-12 isolates were screened for biomass ($9.36gL^{-1}$), TFA ($4.10gL^{-1}$) and DHA (47.01%, w/w) content. C-6 isolates were also screened for biomass ($8.92gL^{-1}$), TFA ($3.30gL^{-1}$) and DHA (49.41%, w/w) content. The 18S rRNA gene sequencing results identified Schizochytrium mangrovei as B-12 and Crypthecodium cohnii as C-6.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.2
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• pp.183-189
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• 2018

Omega-3 unsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found in fish and fish oil. Recent studies have shown that omega-3 fatty acids are effective in cancer, cardiovascular disease, immune system, cirrhosis, and nervous system disorders. In particular, omega-3 was also reported to help improve hyperlipidemia and liver function tests. On the other hand, there are few cases in Korea. This study examined whether omega-3 is effective in improving hyperlipemia and liver function by taking 1 gm/day for 2 weeks. As a result, AST was decreased in the liver function test, and GGT related to alcoholic hepatitis and fatty liver showed significant results. Omega-3 has been shown to help improve the liver function. The triglyceride, total cholesterol, and low density cholesterol associated with cardiovascular disease decreased after omega-3 ingestion, particularly high density cholesterol. Omega-3 has also been shown to improve the hyperlipidemia. Comparisons between males and females before and after the ingestion of omega-3 showed significant results in AST (P<0.01) from the male group and in GGT (P<0.01) and high density cholesterol (P<0.01) from the female group. As a result, omega-3 intake can help control and improve liver function and hyperlipidemia.

• Journal of Life Science
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• v.20 no.4
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• pp.561-571
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• 2010

Colon cancer is one of the most common malignancies in the western world and the second leading cause of cancer death in Korea. Epidemiology studies have shown a reduced incidence of colon cancer among populations consuming a large quantity of ${\omega}3$-polyunsaturated fatty acids (${\omega}3$-PUFA) of marine origin. Recently, it has been found that ${\omega}3$-PUFA has an antineoplastic effect in several cancers. This study was designed to investigate the mechanism of the anti-invasive effect of ${\omega}3$-PUFA in colon cancer. ${\omega}3$-PUFA, docosahexaenoic acids (DHA) and eicosapentaenoic acid (EPA) treatment resulted in a dose-dependent inhibition of cell growth in SW480 human colon cancer cells. In contrast, arachidonic acid (AA), a ${\omega}6$-PUFA, exhibited no significant effect. This action likely involves apoptosis, given that DHA treatment increased apoptotic cells in TUNEL assay. Moreover, invasiveness of SW480 cells was inhibited following treatment of DHA in a dose-dependent manner; in contrast, AA had no effect. The levels of MMP-9 and MMP-2 mRNA decreased after DHA pretreatment. MMP-9 and MMP-2 promoter activities were also inhibited by DHA treatment. The levels of NF-kB and p-IkB protein were down-regulated by DHA pretreatment in a dose dependent manner. In addition, DHA inhibited NF-kB promoter reporter activities. These findings suggest that ${\omega}3$-PUFA may inhibit cancer cell invasion by inhibition of MMPs via reduction of NF-kB in colon cancer. In conclusion, ${\omega}3$-PUFA could be used for chemoprevention and treatment of human colon cancer.

• Molecules and Cells
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• v.42 no.3
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• pp.252-261
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• 2019

The omega-3 fatty acid docosahexaenoic acid (DHA) is known to induce apoptosis and cell cycle arrest via the induction of reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress in many types of cancers. However, the roles of DHA in drug-resistant cancer cells have not been elucidated. In this study, we investigated the effects of DHA in cisplatin-resistant gastric cancer SNU-601/cis2 cells. DHA was found to induce ROS-dependent apoptosis in these cells. The inositol 1,4,5-triphosphate receptor ($IP_3R$) blocker 2-aminoethyl diphenylboninate (2-APB) reduced DHA-induced ROS production, consequently reducing apoptosis. We also found that G-protein-coupled receptor 120 (GPR120), a receptor of long-chain fatty acids, is expressed in SNU-601/cis2 cells, and the knockdown of GPR120 using specific shRNAs alleviated DHA-mediated ROS production and apoptosis. GPR120 knockdown reduced the expression of ER stress response genes, similar to the case for the pre-treatment of the cells with N-acetyl-L-cysteine (NAC), an ROS scavenger, or 2-APB. Indeed, the knockdown of C/EBP homologous protein (CHOP), a transcription factor that functions under ER stress conditions, markedly reduced DHA-mediated apoptosis, indicating that CHOP plays an essential role in the anti-cancer activity of DHA. These results suggest that GPR120 mediates DHA-induced apoptosis by regulating $IP_3R$, ROS, and ER stress levels in cisplatin-resistant cancer cells, and that GPR120 is an effective chemotherapeutic target for cisplatin resistance.

• Journal of Nutrition and Health
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• v.32 no.5
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• pp.577-584
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• 1999

The correlation between maternal lipid nutritional status during pregnancy and gestational length was investigated. Subjects consisted of 30 full-term delivery mothers, 30 preterm delivery mothers, and babies of both groups. Dietary fat intake during pregnancy and serum lipid levels in mother and umbilical serum were measured. The mean daily intake levels of fatty acid during pregnancy were lower than the recommended dietary allowances, while $\omega$6/$\omega$3 ratios of dietary fatty acids were acceptable. For preterm delivery mothers, fatty acid intake levels to be lower than those in full-term delivery mothers, especially DHA intake of these two groups was significantly different. During gestation, hyperlipidemia was apparent in the pregnant women. The serum lipid contents of preterm delivery mothers tended to be lower than those of full-term delivery mothers, and umbilical cord serum lipid contents of the preterm delivery group tended to be higher than those of the full-term delivery group. Total cholesterol levels in the umbilical cord serum of preterm babies were significantly higher than those of full-term delivery group. On the other hand, total cholesterol and HDL-cholesterol levels between umbilical cord serum and maternal serum were positively correlated in the preterm delivery group. Concerning, energy and fatty acid intakes were more closely associated with umbilical cord serum lipid levels in full-term babies, but negatively associated in preterm babies. It was concluded that gestational length was related to the dietary intake of fatty acids such as DHA in pregnant women. For better understanding, the ralationship between placental lipid transport mechanisms and gestational length needs to be explored.

• Journal of Nutrition and Health
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• v.27 no.3
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• pp.215-227
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• 1994

Changes in total lipid content, total cholesterol content and fatty acid composition of preterm milk were investigated during early lactation. Milk samples were collected from Korean mothers of 16 premature(34 to 36 weeks gestation age) infants on day 2 to 5(colostrum) and at 6 weeks(mature) postpartum. We estimated the lipid nutrition of preterm milk by comparing with the lipids of term milk. The total lipid content of preterm colostrum was significantly lower than the lipid content of preterm mature milk(p<0.001). Lipid content, determined gravimetrically in colostrum and matured milk, was 1.50g/이 and 3.2g/dl, respectively. Also the total cholesterol content(mg/dl) in preterm milk tends to increase from 14.16mg/dl to 15.20mg/dl, while the total cholesterol(mg/g lipid) concentration higher significantly in colostrum(12.36mg/g) than in mature(5.73mg/g)(p<0.001). The total unsaturated fatty acid contents in preterm milk were higher in colostrum than in mature milk and the total saturated fatty acids were higher in mature milk. The average DHA contents of colostrum and matured milk was 0.64%, 0.53% and the P/M/S ratio of preterm milk were 0.63 : 1.05 : 1.00, 0.47 : 0.79 : 1.00, respectively. Also, $\omega$6/$\omega$3 ratio of preterm milk were 2.35 in colostrum and 5.81 in mature. Therefore, colostrum in preterm milk contained higher amounts of $\omega$3 PUFA than mature milk. The levels of total lipid in preterm milk were higher than term milk. Also, preterm milk is richer in cholesterol, and long chain polyunsaturated fatty acid than term. It appears that the milk secreted by mothers who delivered prematurely differs from milk in several important respect. These components may serve as precursors for membrane, myelin development in the preterm infants. Therefore, it would be necessary to study further into the machanism of how the gestation age might affect to the lipid composition in human milk. These data may provide a basis for better construction of infant formaulas to provide more adequately for the lipid requirements of the Korean premature infant.

• Korean Journal of Plant Resources
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• v.28 no.1
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• pp.135-144
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• 2015

The Korean daily intake of vegetable oils has increased about 2.5-fold from 17 g/day to 46 g/day for the last several decades. Perilla (Perilla frutescens var. frutescens) has been cultivated in Korea for a long time as a dietary oil seed which has the highest content of ${\alpha}$-linolenic acid, accounting for nearly 60%. It is known that the main role of ALA is as a precursor to the longer-chain ${\omega}-3$, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), the metabolic products of ${\alpha}$-linolenic acid (ALA, ${\omega}-3$). Dietary ${\omega}-3$ fatty acids reduce inflammation and the risk of chronic diseases such as heart disease, cancer, and arthritis, but they also may act as functional components for cognitive and behavioral function. Thus, ${\alpha}$-linolenic acid is one of the essential nutrients in modern dietary patterns in which much linoleic acid is consumed. Nevertheless, perilla oil, rich in ${\alpha}$-linolenic acid, can be easily oxidized, giving rise to controversies with respect to shelf life, the deterioration of the product's commercial value, and further related toxicity. Recent research using genetic modifications has tried to develop new plant oil seeds that balance the ratio of ${\omega}-6/{\omega}-3$ fatty acids. Such trials could be a strategy for improving an easily oxidizable property of perilla oil due to high ${\alpha}$-linolenic acid. Alternatively, appropriate application of antioxidant to the oil can be considerable.

• Journal of Life Science
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• v.23 no.5
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• pp.689-697
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• 2013

In the United States, about 40,000 new cases of oral cancer are diagnosed each year and nearly 7,800 patients died from it in 2012. Omega-3 polyunsaturated fatty acids have been found to have anticancer effects in a variety of cancer cell lines and animal models, but their effect in oral cancer remains unclear. This study was designed to examine the effect of docosahexaenoic acid (DHA, a kind of omega-3 fatty acid) on oral cancer cells and the molecular mechanism of its action. We found that exposure of squamous cell carcinoma-4 (SCC-4) and squamous cell carcinoma-9 (SCC-9) human oral cancer cells to DHA induced growth inhibition in a dose- and time-dependent manner. Meanwhile, in addition to the elevated levels of apoptotic markers, such as cleaved PARP, subG1 portion and TUNEL-positive nuclei, DHA led to autophagic vesicle formation and an increase in autophagic flux, indicating the involvement of both apoptosis and autophagy in the inhibitory effects of DHA on oral cancer cells. Further experiments revealed that the apoptosis and autophagy induced by DHA were linked to inhibition of mammalian target of rapamycin (mTOR) signaling by AKT inhibition and AMP-activated protein kinase (AMPK) activation in SCC-9 cells. Together, our results suggest that DHA induces apoptosis- and autophagy-associated cell death through the AMPK/AKT/mTOR signaling pathway in oral cancer cells. Thus, utilization of omega-3 fatty acids may represent a promising therapeutic approach for chemoprevention and treatment of human oral cancer.

• Food Science of Animal Resources
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• v.43 no.2
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• pp.220-231
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• 2023

Although omega-3 fatty acids including docosahexaenoic acid (DHA) contain various health-promoting effects, their poor aqueous solubility and stability make them difficult to be induced in dairy foods. The aims of this research were to manufacture casein derivative-based delivery system using acid-induced gelation method with glucono-σ-lactone and to investigate the effects of production variables, such as pH and charged amount of linoleic acid, on the physicochemical properties of delivery systems and oxidative stability of DHA during storage in model milk. Covalent modification with linoleic acid resulted in the production of casein derivatives with varying degrees of modification. As pH was reduced from 5.0 to 4.8 and the charged amount of linoleic acid was increased from 0% to 30%, an increase in particle size of casein derivative-based delivery systems was observed. The encapsulation efficiency of DHA was increased with decreased pH and increased charged amount of linoleic acid. The use of delivery system for DHA resulted in a decrease in the development of primary and secondary oxidation products. An increase in the degree of modification of casein derivatives with linoleic acid resulted in a decrease in the formation of primary and secondary oxidation products than of free DHA indicating that delivery systems could enhance the oxidative stability of DHA during storage in model milk. In conclusions, casein derivatives can be an effective delivery system for DHA and charged amount of linoleic acid played a key role determining the physicochemical characteristics of delivery system and oxidative stability of DHA.