Serine palmitoyltransferase inhibitor myriocin induces growth inhibition of B16F10 melanoma cells through G₂/M phase arrest

Lee, Y.‐,S.,Choi, K.‐,M.,Choi, M.‐,H.,Ji, S.‐,Y.,Lee, S.,Sin, D.‐,M.,Oh, K.‐,W.,Lee, Y.‐,M.,Hong, J.‐,T.,Yun, Y.‐,P.,Yoo, H.‐,S. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.4

<P><B>Abstract</B></P><P><B>Objectives: </B> Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti‐cancer treatment have been sought from natural resources. Here, we have investigated anti‐proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the <I>de novo</I> sphingolipid pathway, and its mechanism in B16F10 melanoma cells.</P><P><B>Material and methods: </B> We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate levels were analysed by HPLC.</P><P><B>Results: </B> Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G<SUB>2</SUB>/M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21<SUP>waf1/cip1</SUP> was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate in myriocin‐treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells.</P><P><B>Conclusions: </B> Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21<SUP>waf1/cip1</SUP>, followed by inhibition of cyclin B1 and cdc2, resulting in G<SUB>2</SUB>/M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism‐based therapy for this type of skin cancer.</P>

N-Methyl, N-propynyl-2-phenylethylamine (MPPE), a Selegiline Analog, Attenuates MPTP-induced Dopaminergic Toxicity with Guaranteed Behavioral Safety: Involvement of Inhibitions of Mitochondrial Oxidative Burdens and p53 Gene-elicited Pro-apoptotic Change

Shin, E. J.,Nam, Y.,Lee, J. W.,Nguyen, P. K.,Yoo, J. E.,Tran, T. V.,Jeong, J. H.,Jang, C. G.,Oh, Y. J.,Youdim, M. B. HUMANA PRESS INC 2016 Molecular Neurobiology Vol.53 No.9

<P>Selegiline is a monoamine oxidase-B (MAO-B) inhibitor with anti-Parkinsonian effects, but it is metabolized to amphetamines. Since another MAO-B inhibitor N-Methyl, N-propynyl-2-phenylethylamine (MPPE) is not metabolized to amphetamines, we examined whether MPPE induces behavioral side effects and whether MPPE affects dopaminergic toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Multiple doses of MPPE (2.5 and 5 mg/kg/day) did not show any significant locomotor activity and conditioned place preference, whereas selegiline (2.5 and 5 mg/kg/day) significantly increased these behavioral side effects. Treatment with MPPE resulted in significant attenuations against decreases in mitochondrial complex I activity, mitochondrial Mn-SOD activity, and expression induced by MPTP in the striatum of mice. Consistently, MPPE significantly attenuated MPTP-induced oxidative stress and MPPE-mediated antioxidant activity appeared to be more pronounced in mitochondrial-fraction than in cytosolic-fraction. Because MPTP promoted mitochondrial p53 translocation and p53/Bcl-xL interaction, it was also examined whether mitochondrial p53 inhibitor pifithrin-mu attenuates MPTP neurotoxicity. MPPE, selegiline, or pifithrin-mu significantly attenuated mitochondrial p53/Bcl-xL interaction, impaired mitochondrial transmembrane potential, cytosolic cytochrome c release, and cleaved caspase-3 in wild-type mice. Subsequently, these compounds significantly ameliorated MPTP-induced motor impairments. Neuroprotective effects of MPPE appeared to be more prominent than those of selegiline. MPPE or selegiline did not show any additional protective effects against the attenuation by p53 gene knockout, suggesting that p53 gene is a critical target for these compounds. Our results suggest that MPPE possesses anti-Parkinsonian potentials with guaranteed behavioral safety and that the underlying mechanism of MPPE requires inhibition of mitochondrial oxidative stress, mitochondrial translocation of p53, and pro-apoptotic process.</P>

個人的奢侈品價値與時尙品牌消費的關系: 美國人口特征差異的探索性分析

( Hye Young Kim ),( Jeong Ju Yoo ),( Doo Young Choi ),( Ji Eun Kim ),( K. P. Johnson ) 한국마케팅과학회 2011 Journal of Global Fashion Marketing Vol.2 No.3

Researchers have focused on the explanation that consumers buy luxury brands ``to impress others`` (Tsai, 2005; O``Cass & Frost, 2002; Wiedmann, Hennigs, & Siebels, 2009). Marketers have designed branding strategies that reflect the idea that consumer purchasing is affected by an internal drive to create a favorable social image (Tsai, 2005). However, researchers exploring customer perceptions of and motives for purchasing luxury brands have suggested that socially-oriented motives are insufficient explanations for luxury brand consumption (Wiedmann et al., 2009). These researchers stress that personally- oriented motives have been overlooked in the marketing management of luxury brands. Additionally, empirical research focusing on personal motives is comparatively scarce (Tsai, 2005; Wiedmann et al., 2009). Our study attempted to address this research void by identifying personal luxury values U.S. consumers` associated with their fashion brand consumption. Specific research questions examined were: RQ1: What demographic characteristics are related to personal luxury values? RQ2: What personal luxury values are related to consumers` intentions to purchase luxury fashion brands? A range of motivators can underlie luxury brand consumption. First, some consumers may seek self-directed pleasure from consuming luxury brands and thus their purchase objective has little to do with pleasing peers or social groups (Tsai, 2005). These consumers often buy luxury brands to experience bliss or contentment. Second, self-gift giving could be an important motive that underlies luxury brand consumption. O`Cass and Frost (2002) found that some consumers purchase luxury products as gifts for themselves. Third, a consumer`s self-concept could affect luxury brand consumption. Recently, Wiedmann et al. (2009) confirmed that consumers` perceived congruity of a luxury brand with their self-image or intended self-image is an important variable for segmenting luxury consumers. Building on this fact, consumers may use luxury brands to integrate symbolic meaning into their own identities or they may use the brands to support and develop those identities (e.g., self-completion). Finally, Wiedmann et al. (2009) found that some consumers engaged in luxury brand consumption as a form of self-actualization or life-enrichment. Data were collected using a web survey tool with the help of a marketing research company. Participants were US consumers (n=316) who had purchased a luxury fashion brand in the past three years. Factor analysis with varimax rotation was conducted on 14 personal luxury value items. Items with factor loadings greater than .60 were retained. Two cross-loaded items were dropped resulting in four factors that accounted for 71.1% of the total variance. Item loadings ranged from .64 to .90. Each of the factors had an eigenvalue greater than one. Factor 1 was labeled life enrichment (α=.81) and included four items (e.g., Self-actualization is an important motivator for my luxury fashion brand consumption.). Factor 2 was labeled self-gifting (α=.80) and included three items (e.g., Reward for hard work or that I feel I have earned or am entitled to is an important motivator for my luxury fashion brand consumption.). Factor 3 was labeled self-identity (α=.73) and included three items (e.g., I never buy a luxury fashion brand inconsistent with the characteristics with which I describe myself.). Factor 4 was labeled self-directed pleasure (α=.74) and included two items (e.g., I can enjoy luxury fashion brands entirely on my own terms no matter what others may feel about them.). To answer RQ1, multivariate analysis of covariance (MANCOVA) was employed using income as a covariate. Age (Multivariate F=7.75, p<.001) had the most significant relationship to self-gift giving and life enrichment luxury values. Education (Multivariate F=3.07, p<.05) had a significant relationship with self-identity. Further univariate analysis of covariance (ANCOVA) on age indicated that younger respondents (18-30 years old) showed higher levels of self-gifting (F=25.08, p<.001) and life enrichment (F=18.40, p<.001) values than older consumers (51 or older). ANCOVA analysis on education also revealed that those with a four-year college degree or higher had a higher level of the self-identity value than who did not have a four-year college degree (F=4.69, pp<.05). No main effects were found for gender. However, an interaction effect between gender and education (F=2.76, p<.05) was found for the self-identity value (F=4.29, p<.05). Male respondents with a four-year college degree had a higher level of the self-identity value than females and males who did not have a four-year college degree and females who had at least a four year college degree. No other significant interaction effects were found. Regarding RQ2, the results of hierarchical multiple regression analyses indicated that the following three personal luxury values were significantly related to respondents` intention to purchase luxury fashion brands: self-directed pleasure (β=.25, p<.001), self-gifting (β=.20, p<.001), and self-identity (β=.11, p<.05). By understanding what personal luxury values are sought by American consumers, global luxury fashion marketers could be in a better position: (a) to formulate and implement effective advertising, publicity, special events and personal selling strategies as well as mechanisms of consumer relationship management, and (b) execute marketing programs and activities to build brand images that appeal to and motivate American consumers to purchase.

Late Quaternary transgressive deposits in a low-gradient environmental setting: Korea Strait shelf, SE Korea

Yoo, D.G.,Kim, S.P.,Lee, C.W.,Chang, T.S.,Kang, N.K.,Lee, G.S. Pergamon Press 2014 QUATERNARY INTERNATIONAL Vol.344 No.-

Analysis of high-resolution seismic profiles and sediment data from the Korea Strait shelf reveals that the late Quaternary deposits in this area consist of five sedimentary units deposited during transgression phases of sea-level changes between about 15 and 6 ka BP: ancient beach/shoreface complex (unit P1), estuarine deposits (unit P2), mid-shelf sand sheet (unit M1), sand ridge system (unit M2), and inner-shelf sand sheet (unit M3). They are paralic and marine, separated by a ravinement surface. The lower paralic component below the ravinement surface consists of two sedimentary units (P1 and P2) preserved from shoreface erosion. The top surface of the paralic unit is truncated by a sharp erosional surface. This surface is overlain by three sedimentary units (M1, M2, and M3), which were produced by shoreface erosion that shifted landward during transgression. The transgressive deposits in this area, considering geometries and distribution patterns, can be divided into three types (I, II, and III). Type I overlying the lowstand systems tract is confined to the shelf margin, and consists of a thick paralic unit P1 and a relatively thin marine unit M1. Type II on the mid shelf has no paralic component and the marine units M1 or M2 directly overly the sequence boundary. Type III, found in the inner shelf, includes a thick paralic (unit P2) and a thin marine (unit M3) component. It is completely covered by the highstand systems tract.

Modified Panax ginseng extract regulates autophagy by AMPK signaling in A549 human lung cancer cells

Yoo, H.-S.,Kim, J. M.,Jo, E.,Cho, C.-K.,Lee, S.-Y.,Kang, H. S.,Lee, M.-G.,Yang, P.-Y.,Jang, I.-S. Spandidos Publications 2017 Oncology reports Vol.37 No.6

<P>Panax ginseng has been used worldwide as a traditional medicine for the treatment of cancer and other diseases. The antiproliferative activity of ginseng has been increased after enzymatic processing of ginseng saponin, which may result in the accumulation of minor saponins, such as Rh2, Rg3, compound K and protopanaxatriol type (PPT) in modified regular ginseng extract (MRGX). In the present study, the anticancer activity and the associated mechanisms of MRGX were investigated using A549 human lung cancer cells. To elucidate the mechanisms underlying the effects of MRGX, we performed a microarray analysis of gene expression in the A549 cells. Molecular mechanisms that were associated with the anticancer activity of MRGX were studied, with a special focus on the autophagy-related multiple signaling pathways in lung cancer cells. Microarray analyses elucidated autophagy-related genes affected by MRGX. Administration of MRGX at 100 mu g/ml induced punctate cytoplasmic expression of LC3, Beclin-1 and ATG5 and increased expression of endogenous LC3-II whereas 50 mu g/ml did not inhibit the proliferation of A549 cells. Compared to the control cells, in cells treated with MRGX at 100 mu g/ml, the level of p-Akt was increased, while that of mTOR-4EBP1 was decreased. Downregulation of mTOR and 4EBP1 in the MRGX-treated cells was found not to be a p-Ulk (S757)-dependent pathway, but a p-Ulk (S317)-dependent autophagic pathway, using AMPK. These data suggest that MRGX regulates AMPK and induces autophagy in lung cancer cells.</P>

Circulating TNF receptors predict cardiovascular disease in patients with chronic kidney disease

Bae, Eunjin,Cha, Ran-Hui,Kim, Yong C.,An, Jung N.,Kim, Dong K.,Yoo, Kyung D.,Lee, Su M.,Kim, Myoung-Hee,Park, Jung T.,Kang, Shin-Wook,Park, Jae Y.,Lim, Chun S.,Kim, Yon S.,Yang, Seung H.,Lee, Jung P. Williams & Wilkins Co 2017 Medicine Vol.96 No.19

<P>We prospectively recruited 984 patients with CKD from 11 centers between 2006 and 2012. The levels of cTNFR1 and cTNFR2 were determined by performing an enzyme-linked immunosorbent assay. During the mean follow-up period of 4 years, 36 patients experienced a CVD event. The median serum concentrations of cTNFR1 and cTNFR2 were 2703.4 (225.6-13,057.7) and 5661.0 (634.9-30,599.6) pg/mL, respectively, and the cTNFR1 level was closely correlated with the cTNFR2 level (r=0.86, P < .0001). The urinary protein-to-creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) were significantly correlated with the cTNFR2 level (r=0.21 for UPCR, r=-0.67 for eGFR; P<.001 for all). Similar correlations were observed for serum cTNFR1 (r=0.21 for UPCR, r=-0.75 for eGFR; P < .001 for all). In the Cox proportional hazard analyses, cTNFR1 (hazard ratio [HR] 2.506, 95% confidence interval [CI] 1.186-5.295, P=.016) and cTNFR2 (HR4.156, 95% CI 1.913-9.030, P < .001) predictedCVDrisk even after adjustment for clinical covariates, such as UPCR, eGFR, and high-sensitivity C-reactive protein. cTNFR1 and 2 are associated with CVD and other risk factors in CKD, independently of eGFR and UPCR. Furthermore, cTNFRs could be relevant predictors of CVD in CKD patients.</P>

Effect of Kaposi’s Sarcoma-Associated Herpesvirus (KSHV)-K3 on the Inhibition of Human Natural Killer (N씨 Cell-Mediated Cytl이ysis in Minipig’s Cells

K. W. Park,G. S. Han,K. M. Choi,S. P. Hong,J. Y. Yoo,E. J. Kim,S. H. Kim,Y. C. Park,J. G. Seol 한국동물생명공학회(구 한국동물번식학회) 2008 Reproductive & developmental biology Vol.32 No.2

Effect of Kaposi’s Sarcoma-Associated Herpesvirus (KSHV)-K3 on the Inhibition of Human Natural Killer (NK) Cell-Mediated Cytldlysis in Minipig’s Cells

K. W. Park,G. S. Han,K. M. Choi,S. P. Hong,J. Y. Yoo,E. J. Kim,S. H. Kim,Y. C. Park,J. G. Seol 한국동물번식학회 2008 Reproductive & Developmental Biology(Supplement) Vol.32 No.2s

Effect of Kaposi’s Sarcoma-Associated Herpesvirus (KSHV)-K5 on the Inhibition of Human Natural Killer (NK) Cell-Mediated Cytolysis in Minipig'S Cells

Park K. W.,G,. S. Han,K. M. Choi,S. P. Hong,J. Y. Yoo,E. J. Kim,S. H. Kim,Y. C. Park,J. G. Seol 한국동물번식학회 2007 Reproductive & Developmental Biology(Supplement) Vol.31 No.2s

Effect of Kaposi’s Sarcoma-Associated Herpesvirus (KSHV)-K5 on the Inhibition of Human Natural Killer (NK) Cell-Mediated Cytolysis in Minipig'S Cells

Park K. W.,G,. S. Han,K. M. Choi,S. P. Hong,J. Y. Yoo,E. J. Kim,S. H. Kim,Y. C. Park,J. G. Seol 한국동물생명공학회(구 한국동물번식학회) 2007 Reproductive & developmental biology Vol.31 No.2