Korea Science And Engineering Foundation Research Articles

Korean Traditional Fermented Soybean Paste (Doenjang) Regulate Renin-Angiotensin System (RAS) in 3T3-L1 Adipocytes

Abstract Objectives Doenjang, the Korean traditional fermented soybean paste, contains much salt. There is a concern that cardiovascular disease may occur due to such high salinity. Nevertheless, previous studies have demonstrated functional properties of doenjang anti-obesity and anti-cancer effects. Furthermore, in our recent studies, we showed that the anti-hypertensive effect of doenjang through renin-angiotensin system (RAS) regulation. Doenjang regulated the RAS to improve lipid metabolism in adipose tissue, which had a positive effect on blood pressure control. Therefore, we expected to find the exact mechanism of action or target point of doenjang in adipocyte using 3T3-L1 cells. Methods In this study, 3T3-L1 cells were treated with doenjang and RAS blockers, Losartan (10−4 M), and Captopril (10−4 M), were treated as positive control which suppresses AT1R and ACE, respectively. Non-cytotoxic concentrations of samples were selected as per MTT assay and added with induction media, harvested after 4 days for RNA extraction. Lipid droplets were detected by Oil Red O staining. Results Doenjang downregulated mRNA levels of peroxisome proliferator-activated receptor-γ (Pparg), RAS related genes such as angiotensinogen (Agt), Renin (Ren), and aldosterone-releasing factors (P < 0.05). Especially, angiotensin convert enzyme (Ace) and angiotensin II receptor 2 (Agtr2) levels were decreased by doenjang treatment. Doenjang reduced the lipid accumulation, which was confirmed from the Oil Red O staining of lipid droplets. As a result, it is revealed that doenjang not only inhibits lipid accumulation in adipocytes but also may inhibit ACE in 3T3-L1 adipocytes through a mechanism similar to the effect of Captopril. Conclusions These data are consistent with our animal study. It have been shown to regulate blood pressure through lipid improvement and ACE inhibition despite high salt content in doenjang. Funding Sources This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. 2018R1A2B6006477).

“목적 있는 기초 연구”: 한국과학재단 설립 이후 기초 연구 외연의 확장, 1977-1989

The Korea Science and Engineering Foundation (KOSEF) was established in 1977 to promote universities and encourage basic research. This article focuses on the projects of KOSEF and the discourse surrounding the concept of “basic research.” Observing the changing concept of “basic research” and the role of universities in the 1970s and 1980s will allow one to understand the perspective of the Korean government, especially the Ministry of Science and Technology(MOST). This paper will show that the Korean government’s plan to integrate higher education institutions in the process of national development was inextricably linked to its notion of “basic research.” Through this process, South Korean universities were able to play significant roles as research institutes after the 1990s. During the 1980s, the concept of “basic research” was expanded to include areas of applied science and engineering, and the Korean government wanted the universities to take part in national development by conducting research in these areas. The “mission-oriented basic research project” became the largest project within KOSEF after the mid-1980s in order to actively engage universities in those areas of research.

Association between Dissociative Symptoms and Morning Cortisol Levels in Patients with Post-Traumatic Stress Disorder

Background: Patients with post-traumatic stress disorder (PTSD) showed inconsistencies in their cortisol level, an index of the hypothalamic-pituitary-adrenal (HPA) axis function. This study examined the relationship between dissociation, childhood trauma, and morning cortisol levels in PTSD patients. Methods: This study included 69 patients and 82 healthy controls (HCs). Clinical assessments, including the Childhood Trauma Questionnaire (CTQ) and Peri-traumatic Dissociative Experiences Questionnaire scores (PDEQ), and morning cortisol levels were evaluated. The morning cortisol levels were compared between PTSD with high dissociation (PTSD-HD) and low dissociation (PTSD-LD) groups. The effect of CTQ subtype on morning cortisol levels was analyzed. Outcomes: The PTSD-HD group showed significantly lower cortisol levels than that of the PTSD-LD and HC groups. A significant inverse correlation was found between morning cortisol levels and dissociation. A significant positive correlation was found between dissociation and physical abuse and sexual abuse scores. Morning cortisol levels showed significant positive correlation with emotional abuse, emotional neglect, and physical neglect. There was no moderating or mediating effect of childhood traumatic experience on the relationship between cortisol levels and dissociation. Interpretation: These findings suggest that dissociation is a significant factor related to hypocortisolism in PTSD patients. Additionally, basal morning cortisol levels and dissociation scores were closely associated with the childhood trauma. Funding Statement: This study was supported by a grant from the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (NRF-2015M3C7A1028252), and a grant from the Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (NRF2018R1A2A2A05018505). Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: All participants signed an informed consent form approved by the Institutional Review Board before participating (IRB no. 2015-07-025).

Renin-angiotensin System (RAS)-mediated Antiobesity and Antihypertensive Effects of Korean Traditional Soybean Paste (Doenjang) in Rat Model of Diet-induced Obesity (P08-097-19)

Abstract Objectives Hypertension is becoming more prevalent and one of the main cause is found in the increase of excessive dietary sodium intake. It is also risk factors for cardiovascular and kidney disease. Korean Traditional Fermented Food, doenjang, is made with high salt, so many of them are thinking that there is a lot of relation to hypertension despite reporting many health benefits. Our previous studies reported that doenjang have been associated effect of anti-obesity in human and animal study. Therefore, we expected that doenjang may have different effects on blood pressure and lipid metabolism compared to same concentrations of salt. Methods In this study, Sprague-Dawley rats divided into four groups, normal diet (ND), high fat diet (HD), high fat diet with 8% table salt (HDS), high fat diet with Doenjang contains 8% table salt (HDJ) for 13 weeks. The systolic blood pressure (SBP), serum chemistry, Na+ and K+ concentrations, liver and renal gene expressions were measured. Results Doenjang decreased systolic blood pressure (SBP), body weight and hepatic lipids. Serum chemistry, leptin and aldosterone levels were increased in HD and HDS groups while decreased in HDJ group. Results from analysing feces and urine, Na+, Ca+ and K+concentrations were changed by Doenjang. Furthermore, fatty acid synthesis-related genes expression was decreased in liver and downregulated the renin, AT1 receptor and ACE in renal cortex of doenjang treatment group. Conclusions These results suggest that doenjang may have anti-obesity and anti-hypertension through regulation of the renin angiotensin system. We believed that it is an important result of demonstrating that doenjang has health benefits regardless of salt content. Funding Sources This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. 2018R1A2B6006477).

Dynamic Capabilities of Project-Based Organization in Global Operations

This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant and funded by the Korean government (NRF-2015R1A2A1A09007327). This research was partially supported by The George Washington University’s Center for International Business Education and Research (GW-CIBER).

SU‐E‐J‐67: Evaluation of Breathing Patterns for Respiratory‐Gated Radiation Therapy Using Respiration Regularity Index

Purpose:Despite the importance of accurately estimating the respiration regularity of a patient in motion compensation treatment, an effective and simply applicable method has rarely been reported. The authors propose a simple respiration regularity index based on parameters derived from a correspondingly simplified respiration model.Methods:In order to simplify a patient's breathing pattern while preserving the data's intrinsic properties, we defined a respiration model as a power of cosine form with a baseline drift. According to this respiration formula, breathing‐pattern fluctuation could be explained using four factors: sample standard deviation of respiration period, sample standard deviation of amplitude and the results of simple regression of the baseline drift (slope and standard deviation of residuals of a respiration signal. Overall irregularity (δ) was defined as a Euclidean norm of newly derived variable using principal component analysis (PCA) for the four fluctuation parameters. Finally, the proposed respiration regularity index was defined as ρ=ln(1+(1/ δ))/2, a higher ρ indicating a more regular breathing pattern. Subsequently, we applied it to simulated and clinical respiration signals from real‐time position management (RPM; Varian Medical Systems, Palo Alto, CA) and investigated respiration regularity. Moreover, correlations between the regularity of the first session and the remaining fractions were investigated using Pearson's correlation coefficient.Results:The respiration regularity was determined based on ρ; patients with ρ<0.3 showed worse regularity than the others, whereas ρ>0.7 was suitable for respiratory‐gated radiation therapy (RGRT). Fluctuations in breathing cycle and amplitude were especially determinative of ρ. If the respiration regularity of a patient's first session was known, it could be estimated through subsequent sessions.Conclusions:Respiration regularity could be objectively determined using a respiration regularity index, ρ. Such single‐index testing of respiration regularity can facilitate determination of RGRT availability in clinical settings, especially for free‐breathing cases.This work was supported by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean Ministry of Science, ICT and Future Planning (No. 2013043498).

Involvement of AMPK in the regulation of CSK, COX‐2 and mTOR in cancer cell growth control under EGCG treatment

Epigallocatechin gallate (EGCG) was recently shown to activate the AMP‐activated protein kinase (AMPK) in cancer cells and in vivo systems. In the lieu of elucidating the mechanism for this effect and the consequence of the activation of AMPK on the important signals of cancer cell control‐CSK, COX‐2 and mTOR, we have applied Hep3B and HT‐29 cancerous cells. We have shown that EGCG activated AMPK possibly through stimulation of AMPK. The activation of AMPK with EGCG suppressed the expression of CSK as well as COX‐2 and mTOR. EGCG induced the translocation of AMPK into nucleus. Upon the inactivation of AMPK either by AMPK siRNA or Compound C, EGCG no longer modulated CSK or COX‐2 or mTOR implying that AMPK is an upstream signal for these molecules. With fluorescent markers of AMPK, CSK and COX‐2 with or without the activation of AMPK, it was shown that EGCG stimulated the translocation of AMPK and CSK into the nucleus. However, without the activation of AMPK via Compound C, the stimulatory effect of EGCG on the translocation into the nucleus was diminished. Therefore, the activation of AMPK and the translocation of AMPK into the nucleus seem to be necessary for EGCG to control cancer cell growth and further the regulation of CSK, COX‐2 and mTOR. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (NO. R01‐2008‐000‐20131‐0)]Grant Funding Source: Korea Science and Engineering Foundation

Flapless Dental Implant Surgery may Improve Hard and Soft Tissue Outcomes

A 1-year prospective clinical study of soft tissue conditions and marginal bone changes around dental implants after flapless implant surgery. Jeong S-M, Choi B-H, Kim J, Xuan F, Lee D-H, Mo DY, etal. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;111:41-6. Richard Oliver, BDS, BSc, PhD, FDSRCPS, FDS(OS)RCPS PURPOSE/QUESTION: To evaluate the soft tissue and marginal bone levels after 1 year around dental implants placed using flapless surgery Korea Science and Engineering Foundation (KOSEF) funded by the Korean Government Case series Level 3: Other evidence Grade C: Consensus, disease-oriented evidence, usual practice, expert opinion, or case series for studies of diagnosis, treatment, prevention, or screening.

Characteristics of a Photonic Crystal Structure Made by Flow-controlled Vertical Deposition Method

This work was supported by the Korea Science and Engineering Foundation (KOSEF) through the Quantum Photonic Science Research Center at Hanyang University and through the Basic Research Support program under contract No. 2009-0073641.

Abstract 274: PGC-1α over-expression is related to increased cell proliferation and tumorigenesis

Abstract Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a coactivator interacting with multiple transcription factors and regulates several metabolic processes. Recent studies have focused on the role of several coactivators in cancer. Especially, a role of PGC-1α in cancer has been controversial. Some studies show that the expression level of PGC-1α decreased in certain cancer tissues and PGC-1α over-expression induces apoptosis in ovarian cancer cells. On the contrary, it has been found that PGC-1α promotes cell growth in prostate cancer cells, suggesting that PGC-1α may be involved in the pathogenesis of cancer. However, the molecular mechanism for it has not been clarified. Thus, the role of PGC-1α in the cell proliferation and tumorigenesis was evaluated using human embryonic kidney HEK293 cells that stably over-expressed PGC-1α. Forced expression of PGC-1α in HEK293 cells resulted in increased cell proliferation and anchorage-independent growth in soft agar. In addition, HEK293 cells that highly expressed PGC-1α enhanced tumor formation when these cells are subcutaneously injected into the bilateral flanks of immunodeficient Balb/c mice. To find out the molecular targets for increased proliferation and tumorigenesis by PGC-1α, GeneFishing DEG screening system was employed. As a result, one up-regulated gene (acyl-CoA binding protein; ACBP) was identified. Up-regulated ACBP expression was confirmed by Western blot and immunofluorescence microscopy. The expression of ACBP was decreased by PGC-1α siRNA transfection. These data suggest that the expression of ACBP may be related to the expression of PGC-1α. In addition, down-regulation of ACBP and PGC-1α by siRNA transfections resulted in the decreased cell proliferation. Taken together, these findings suggest that PGC-1α may promote cell proliferation and tumorigenesis. Thus, PGC-1α can be a good candidate for a molecular therapeutic target for cancers. However, the detailed molecular mechanisms for up-regulation of ACBP by PGC-1α are remained unresolved. Thus, further studies on the clarification of molecular interactions of ACBP and PGC-1α are needed. This study was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) through the Medical Research Center for Cancer Molecular Therapy at Dong-A University (R13-2002-044-05002-0). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 274. doi:10.1158/1538-7445.AM2011-274

The Effect of Potassium Chloride in Rat Wound Healing

This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (No. R01-2007-000-20746-0).

Role of Amblyomin-X on microcirculatory vessels, endothelial cell migration and tumor growth

Role of Amblyomin-X on microcirculatory vessels, endothelial cell migration and tumor growth

MicroRNA/Argonaute 2 regulates nonsense‐mediated messenger RNA decay

Imperfect base-pairing between microRNA (miRNA) and the 3'-untranslated region of target messenger RNA (mRNA) triggers translational repression of the target mRNA. Here, we provide evidence that human Argonaute 2 targets cap-binding protein (CBP)80/20-bound mRNAs and exon junction complex-bound mRNAs and inhibits nonsense-mediated mRNA decay (NMD), which is restricted tightly to CBP80/20-bound mRNAs. Furthermore, microarray analyses reveal that a subset of cellular transcripts, which are expected to be targeted for NMD, is stabilized by miRNA-mediated gene silencing. The regulation of NMD by miRNAs will shed light on a new post-transcriptional regulation mechanism of gene expression in mammalian cells.

Abstract LB-167: Identification of ionizing radiation (IR)-responsive mRNA in p53-deficient human non-small cell lung cancer (NSCLC) grown in three-dimensional cell culture system

Abstract Non-small cell lung cancer (NSCLC) has been known as the most common human malignancy. The p53 tumor suppressor gene is mutated in approximately 50 % of NSCLC. For treatment of lung cancer, radiotherapy using -ray is general treatment. However, many patients suffer from recurred disease. Therefore, the definite mechanism of radiation based on in vivo mimic system is required for effective remedical value to NSCLC. Most of radiation biology studies were performed in conventional monolayer culture system which can not represent in vivo tumor environment. Hence, study applying in vivo mimic three-dimensional culture system is necessary to elucidate the molecular mechanism of solid tumor. Here, we analyzed gene expression profile induced by ionizing radiation (IR) in H1299 cells grown as spheroid in three-dimensional cell culture system. Our data showed that different gene expression profiles among monolayer culture system, three-dimensional small spheroid and three-dimensional large spheroid system. Particularly, genes related with microenvironment including adhesion junction and hypoxia had different expression level in three-dimensional spheroid system compare with monolayer culture system. This study suggested that in vivo mimic three-dimensional cell culture engineering approach might provide critical clues for understanding of cellular responses in p53 mutated or deleted lung cancer cells against IR. (* This work was supported by Nuclear Research Development Program of the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korean government (MEST). (Grand code: 2007-2001431, 2008-2001694, 2009-0078295) from Korea Science and Engineering Foundation) Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-167.

Abstract 4439: Anti-cancer actions of omega-3 polyunsaturated fatty acids in human cervical cancer

Abstract Over 90% of human cervical carcinoma is associated with high risk human papillomavirus (HPV), and a number of biological effects that could contribute to cancer suppression by ω3-polyunsaturated fatty acids (ω3-PUFAs) have been reported. However, the anti-cancer effect of ω3-PUFAs on cervical cancer has been not known yet. In this study, we report inhibitory mechanisms of ω3-PUFAs on cell growth and invasion in cervical cancer. DHA inhibited the cell growth in a dose- and time-dependent manner. In flow cytometry analysis, cell cycle of DHA-treated HeLa cells was arrested in G2/M phase and SubG1 cells also increased. Moreover, apoptotic cell death was confirmed by TUNEL assay, the induction of PARP cleavage and down-regulation of Bcl-2. The invasiveness of cells was significantly inhibited by DHA treatment in vitro transwell assay as well. The MMP-9 and MMP-2 promoter activities were decreased after DHA treatment. Cox-2 and VEGF promoter activities were also inhibited by DHA. Furthermore, DHA decreased the levels of reporter activity of NF-κB, which is transcription factor that regulates MMPs, Cox-2 and VEGF expression. In in vivo experiments, when human papillomavirus type 16 (HPV16)-transformed mouse TC-1 cells were injected into the tail vein of Fat1 mice (Fat1 transgenic mice express a Caenorhabditis elegans ω3-desaturase converting ω6- to ω3-PUFAs endogenously.) and WT (wild type) mice, lung metastasis of TC-1 cells was dramatically inhibited in Fat1 transgenic mice compared to WT mice. Taken together, these findings provide evidence that ω3-PUFAs may inhibit metastasis as well as cell growth and invasion through suppression of MMPs/COX-2/VEGF expression by inhibition of NF-κB expression in cervical cancer cells, indicating that the utilization of ω3-PUFAs may represent a potential effective therapy for the chemoprevention and treatment of human cervical cancer.[This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government(MEST) (#E00026) and by the Infection Signaling Network Research Center (R13-2007-020-01000-0) at Chungnam National University]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4439.

Abstract 458: A novel resveratrol analogue, HS-1793, down-regulates the expression levels of hypoxia-inducible factor-1α and VEGF, and inhibits hypoxia-induced cell migration of human prostate cancer cells

Abstract Hypoxia-inducible factor-1α (HIF-1α), a transcription factor, over- expressed in many human tumors and their metastases, and is closely associated with more aggressive tumor phenotype. An important objective of anti-cancer therapy is the development of new drugs that suppress hypoxic responses in solid tumors. In many studies, resveratrol has been shown to chemopreventive effect in various cancer cells. However, resveratrol's biological activity is limited by its photosensitivity and metabolic instability. This study was investigated the effects of a novel analogue of resveratrol, HS-1793, on the expression levels of HIF-1α and vascular endothelial growth factor (VEGF) in PC-3 human prostate cancer cells. Hypoxic condition induced a time-dependent increase in the level of HIF-1α protein in PC-3 cells, and treatment with HS-1793 markedly decreased HIF-1α expression level. HS-1793 also inhibited VEGF expression level. Mechanistically, HS-1793 inhibited HIF-1α and VEGF expression through multiple mechanisms. Firstly, HS-1793 inhibited both PI3K and Erk phosphorylations in PC-3 cells. Secondly, HS-1793 substantially induced HIF-1α protein degradation through the proteasome pathway. Finally, HS-1793 inhibited hypoxia-induced cell migration. These data suggested that HS-1793 may inhibit human prostate cancer progression and angiogenesis by inhibiting HIF-1α and VEGF expression. Moreover, HS-1793 showed more potent effect than resveratrol on the cytotoxic effects on PC-3 cells. Taken together, these results implied that HS-1793, a novel analogue of resveratrol, might be a new potent chemopreventive agent against human prostate cancer cells. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R01-2006-000-11117-0)]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 458.

Abstract 4441: Stichoposides induce apoptosis through the generation of ceramide in human leukemia cells

Abstract Marine triterpene glycosides are physiologically active natural compounds, isolated from sea cucumbers (holothurians) and demonstrate a wide spectrum of biological effects. Stichoposides are extracted from Thelenota anax (family Stichopodidae). Previous studies demonstrated that stichoposides had antifungal, cytotoxic, and antitumor activities. However, the specific molecular mechanisms underlying this effect remain to be elucidated. Stichoposide-induced apoptosis was examined in human leukemia cells in relation to mitochondrial injury and perturbations in signaling pathways. Stichoposide C (STC) induces apoptosis in these cells in a dose-dependent manner and leads to the activation of FAS, recruitment of FADD, activation of caspase-8, cleavage of Bid, mitochondrial damage and activation of caspase-3. In contrast, stichoposide D (STD) induces apoptosis in these cells in a dose-dependent manner and causes to activation of extrinsic pathway, not to activation of intrinsic pathway. In addition, STC- and STD-induced apoptosis are mediated by ER stress pathway, showing that Salubrinal, ER pathway inhibitor, inhibits apoptosis by STC and STD. STD activated acid sphingomyelinase (SMase) and neutral SMase, resulting in the generation of ceramide, but STC slightly activated them. By using specific inhibitor for acid SMase or neutral SMase and siRNA knockdown experiments, stichoposides-induced apoptosis was blocked. Thus, these results indicate that ceramide generation by stichoposides may contribute to stichoposides-induced apoptosis. Thus, these data suggest that stichoposides may have therapeutic relevance in the treatment of human leukemia. This study was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) through the Medical Research Center for Cancer Molecular Therapy at Dong-A University (R13-2002-044-05002-0). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4441.

Abstract 4457: Omega-3 polyunsaturated fatty acids induce apoptosis cell death and inhibit LPS-induced invasion in PC3 cells

Abstract Dietary fat as a potential risk factor for cancer has been the focus of many epidemiologic and basic researchers, but the findings have been inconclusive. Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. In this study, we have investigated anticancer action of ω3-PUFAs and effect of ω3-PUFAs on LPS-mediated TLR4 signaling in prostate cancer. DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) treatment resulted in a dose-dependent reduction of cell viability with apoptosis of PC3 cells as confirmed by TUNEL assay. In contrast, AA (arachidonic acid), a ω6-PUFA, exhibited no significant effect. Moreover, invasiveness of PC3 cells was inhibited in a dose-dependent manner by treatment of DHA, while AA showed no significant effect. In zymography, MMP-2 activity was inhibited by DHA treatment and MMP-9 and MMP-2 promoter activities were also inhibited. DHA inhibited Cox-2 and VEGF promoter activities and NF-kB reporter activity was also decreased. The expression of TLR4 was confirmed by RT-PCR in PC3 cells and DHA dramatically inhibited the LPS-induced invasion of PC3 cells. In in vivo experiments, when mouse prostate cancer cells (RM1) were injected into the tail vein of Fat1 mice (Fat1 transgenic mice express a Caenorhabditis elegans ω3-desaturase converting ω6- to ω3-PUFAs endogenously.) and WT (wild type mice), lung metastasis was significantly inhibited in Fat1 transgenic mice compared to WT mice. In conclusion, the present study suggests that ω3-PUFAs may inhibit prostate cancer cell growth, and invasion through decrease of MMPs, Cox-2, VEGF and NF-kB reporter activities. Moreover LPS-mediated invasiveness was inhibited by DHA. These findings provide important preclinical evidence and molecular insight for utilization of ω-3 PUFAs for the chemoprevention and treatment of human prostate cancer. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Infection Signaling Network Research Center (R13-2007-020-01000-0) at Chungnam National University]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4457.

Abstract 226: Aspirin alone or in combination with doxorubicin induced efficient apoptosis in human hepatocellular carcinoma cells

Abstract Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is refractory to most anticancer drugs. Doxorubicin offers a survival benefit to patients with intermediate hepatocellular carcinoma. However, the favorable therapeutic response to doxorubicin is often associated with severe toxicity. The present research was aimed at developing a strategy of increasing doxorubicin sensitivity so that lower doses may be used without compromising efficacy. Recently, aspirin (ASA) and some other nonsteroidal anti-inflammatory drugs (NSAIDs) have drawn much attention for their protective effects against colon cancer and cardiovascular disease. Several studies also found that regular ASA use is significantly associated with reduced risk of lung cancer. We investigated the effects of ASA on HepG2 human hepatocellular carcinoma cell line. Growth inhibition effect of aspirin was measured by MTT assay. Flow cytometry analysis revealed that aspirin can induce G2/M phase arrest which we observed by the level of cell cycle regulatory proteins and DNA ladder formation indicates apoptosis dose dependently. We found that ASA treatment followed both extrinsic and intrinsic pathways for apoptosis induction. In addition to this, when administered in combination, doxorubicin (DOX) and ASA produced synergistic effect in growth inhibition in human hepatocellular carcinoma cells and induced apoptosis in caspase-dependent pathway. Therefore, clinically achievable concentrations of DOX and ASA used in combination may produce a strong anticancer synergy that warrants investigation as a therapeutic strategy to enhance the efficacy of doxorubicin for treating HCC. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R01-2006-000-11117-0)]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 226.

Gene expression in the brain from antidepressants treated mouse using DNA microarray

The molecular and biological bases for the mechanisms of antidepressants are based on the monoamine depletion hypothesis. However, we do not yet know the full cascade of mechanisms responsible for the therapeutic effect of antidepressants. To identify the genes involved in the therapeutic mechanisms of various antidepressants, we used a cDNA microarray system containing 30000 clones with isolated total RNA from each treated rat brain. In the present study, we demonstrated gene expression changes of treatment with a tricyclic antidepressant (imipramine), a selective serotonin reuptake inhibitor (fluoxetine), monoamine oxidase inhibitor (phenelzine) and psychoactive herbal extracts of PM011. The expression of 35, 20, 37 and 44 genes were decreased and 21, 49, 35 and 27 were over‐expressed by imipramine, fluoxetine, phenelzine and PM011, respectively.Members of signal transduction, factors related to protein metabolism, cell survival, ligand‐receptor interaction, were some of the genes with altered expression. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism.The results support the hypothesis that the therapeutic effect of these antidepressants is much more complex and not confined to a reuptake inhibition of neurotransmitters and inhibition of MAOThis work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government(MEST) (No. 2009‐0063466).