The tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer agent due to its unique ability to induce cancer cell death having only negligible effects on normal cells. However, many cancer cells tend to be resistant to TRAIL. In this study, we investigated the effects and molecular mechanisms of sodium butyrate (SB), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in 5637 human bladder cancer cells. Our results indicated that co-treatment with SB and TRAIL significantly increased the apoptosis induction, compared with treatment with either agent alone. Co-treatment with SB and TRAIL effectively increased the cell-surface expression of death receptor (DR) 5, but not DR4, which was associated with the inhibition of cellular Fas-associated death domain (FADD)-like interleukin-1β-converting enzyme (FLICE) inhibitory protein (c-FLIP). Furthermore, the activation of caspases (caspase-3, -8 and -9) and degradation of poly(ADP-ribose) were markedly increased in 5637 cells co-treated with SB and TRAIL; however, the synergistic effect was perfectly attenuated by caspase inhibitors. We also found that combined treatment with SB and TRAIL effectively induced the expression of pro-apoptotic Bax, cytosolic cytochrome c and cleave Bid to truncated Bid (tBid), along with down-regulation of anti-apoptotic Bcl-xL expression. These results collectively suggest that a combined regimen of SB plus TRAIL may offer an effective therapeutic strategy for safely and selectively treating TRAIL-resistant bladder cancer cells.
Kang, Kyeong-Rok;Kim, Jae-Sung;Kim, Tae-Hyeon;Seo, Jeong-Yeon;Park, Jong-Hyun;Lim, Jin Woong;Yu, Sun-Kyoung;Kim, Heung-Joong;Shin, Sang Hun;Park, Bo-Ram;Kim, Chun Sung;Kim, Do Kyung
International Journal of Oral Biology
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v.45
no.3
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pp.107-114
/
2020
Acacetin, which is present in damiana (Turnera diffusa) and black locust (Robinia pseudoacacia), has several pharmacologic activities such as antioxidant, anti-inflammatory, and anti-proliferative effects on cancer cells. However, the effect of acacetin on head and neck cancers has not been clearly established. This study aimed to examine the effects of acacetin on cell growth and apoptosis induction in FaDu human pharyngeal carcinoma cells. These were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, Live/Dead cell assay, 4',6-diamidino-2-phenylindole dihydrochloride staining, caspase-3 and caspase-7 activation assay, and immunoblotting in FaDu cells. Acacetin induced FaDu cell death in a dose-dependent manner, with an estimated IC50 value of 41.9 µM, without affecting the viability of L-929 mouse fibroblasts as normal cells. Acacetin treatment resulted in nuclear condensation in the FaDu cells. It promoted the proteolytic cleavage of procaspase-3, -7, -8, and -9 with increasing amounts of the cleaved caspase isoforms in FaDu cells. Acacetin-induced apoptosis in FaDu cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting showed downregulation of the anti-apoptotic mitochondrial proteins Bcl-2 and Bcl-xL, but upregulation of the mitochondria-dependent pro-apoptotic proteins Bax and Badin FaDu cells after acacetin treatment. These findings indicate that acacetin inhibits cell proliferation and induces apoptotic cell death in FaDu human pharyngeal carcinoma cells via both the death receptor-mediated extrinsic apoptotic pathway and the mitochondria-mediated intrinsic apoptotic pathway.
Two feeding experiments were conducted to investigate the effects of dietary genetically modified (GM) soya and com on growth performance, feed utilization and body composition of juvenile olive flounder, Paralichthys olivaceus and rockfish, Sebastes schlegelii. For each fish species, four isonitrogenous (50% crude protein) and isocaloric (4.1 kcal/g) diets (designated as nGM soya, GM soya, nGM com and GM com) were formulated to contain 20% non-GM (nGM) and GM soya and com. Thirty olive flounder (initial body weight, 15.4${\pm}$0.4 g) and fifty rockfish (initial body weight, 3.1${\pm}$0.02 g) were distributed in each 400 L tank (200 L water) in a flow through system. Each experimental diet was fed to triplicate groups of fish to visual satiation, twice a day (9:00 hand 17:00 h) for 6 weeks. Growth performance was measured every three weeks. No effects of GM feedstuffs on survival were observed. Dietary inclusion of GM feedstuffs did not affect growth performance and feed utilization of fishes, except for rockfish fed GM com. Rockfish fed the GM com diet showed higher weight gain, daily feed intake and daily protein intake than did fish fed the nGM com diet, but no significant differences were observed in final body weight between the dietary treatments. Condition factor, hepatosomatic index, visceral somatic index and body composition were not altered by the inclusion of GM feedstuffs. These results indicate that dietary inclusion of GM soya and com could have no effects on growth performance and feed utilization of juvenile flounder and rockfish. Lower weight gain and feed intake in flounder and rockfish fed the diets containing 20% soya were likely due to anti-nutritional factors, rather than transgenic factors in the feedstuffs. Dietary inclusion of GM soya and com at the level tested did not alter the body composition of fishes. Further studies to investigate the effects of GM feedstuffs on health conditions and the development of fishes, as well as those of residue of transgenic fragments in ambient environments and in animals are necessary for safe use of the ingredients in aquaculture.
Anti-obese effects of mulberry (Morus alba L.) root bark was investigated in vitro by measuring its inhibitory effect against 3T3-L1 preadipocyte differentiation and digestive enzymes such as ${\alpha}$-amylase, ${\alpha}$-glucosidase and pancreatic lipase. Ethanol extract of mulberry root bark (MRE) showed the potent inhibitory activities on ${\alpha}$-amylase, ${\alpha}$-glucosidase and pancreatic lipase with $IC_{50}$ values of $7.86{\pm}0.36$, $0.12{\pm}0.03$ and $7.93{\pm}0.11mg/mL$, respectively. Furthermore, MRE significantly suppressed cellular lipid accumulation in 3T3-L1 cells in a dose-dependent manner. To elucidate the mechanism of MRE, we performed qRT-PCR and Western blotting for the expression of genes related with adipogenesis and lipogenesis. Treatment of MRE markedly suppressed the protein expression of $PPAR{\gamma}$, $C/EBP{\alpha}$ and SREBP-1c, as well as FAS and ACC, which are the key transcription factors and metabolic enzymes in adipogenesis and lipogenesis. In addition, qRT-PCR analysis indicated that the anti-adipogenesis effect of MRE might be due to its inhibition at transcription levels. These results demonstrate that MRE can effectively suppress adipocyte differentiation and inhibit key enzymes related to obesity. Our findings suggest that mulberry root bark may have a potential benefit in preventing obesity.
Kwak, Chung Shil;Kim, Mi-Ju;Kim, Sun Gi;Park, Sunyeong;Kim, In Gyu;Kang, Heun Soo
Journal of Nutrition and Health
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v.52
no.6
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pp.529-539
/
2019
Purpose: Sprouts of evening primrose (Oenothera laciniata, OL) were reported to have high contents of flavonoids and potent antioxidant activity. This study examined the antioxidant and antiobesity activities of OL sprouts to determine if they could be a natural health-beneficial resource preventing obesity and oxidative stress. Methods: OL sprouts were extracted with 50% ethanol, evaporated, and lyophilized (OLE). The in vitro antioxidant activity of OLE was examined using four different tests. The antiobesity activity and in vivo antioxidant activity from OLE consumption were examined using high fat diet-induced obese (DIO) C57BL/6 mice. Results: The IC50 for the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging and superoxide dismutase (SOD)-like activities of OLE were 26.2 ㎍/mL and 327.6 ㎍/mL, respectively. OLE exhibited the ferric reducing antioxidant power (FRAP) activity of 56.7 ㎍ ascorbic acid eq./mL at 100 ㎍/mL, and an increased glutathione level by 65.1% at 200 ㎍/mL compared to the control in the hUC-MSC stem cells. In an animal study, oral treatment with 50 mg or 100 mg of OLE/kg body weight for 14 weeks reduced the body weight gain, visceral fat content, fat cell size, blood leptin, and triglyceride levels, as well as the atherogenic index compared to the high fat diet control group (HFC) (p < 0.05). The blood malondialdehyde (MDA) level and the catalase and SOD-1 activities in adipose tissue were reduced significantly by the OLE treatment compared to HFC as well (p < 0.05). In epididymal adipose tissue, the OLE treatment reduced the mRNA expression of leptin, PPAR-γ and FAS significantly (p < 0.05) compared to HFC while it increased adiponectin expression (p < 0.05). Conclusion: OLE consumption has potent antioxidant and antiobesity activities via the suppression of oxidative stress and lipogenesis in DIO mice. Therefore, OLE could be a good candidate as a natural resource to develop functional food products that prevent obesity and oxidative stress.
Hwang, Dae Il;Choi, In-Ho;Kim, Do Yoon;Park, Soo Min;Kim, Ha Bin;Li, YaLi;Lee, Hwan Myung
Journal of Life Science
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v.29
no.3
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pp.332-336
/
2019
Obesity is associated with an increased risk of many diseases including type 2 diabetes mellitus, hypertension, and hyperlipidemia. The flowers of Chrysanthemum boreale have been used as traditional medicines for the treatment of diseases such as obesity and type 2 diabetes mellitus. This study aimed to evaluate the effect of C. boreale Makino flower essential oil (CFEO) on adipocyte differentiation using preadipocyte cell line 3T3-L1. CFEO at concentrations between 0.1 and $5{\mu}g/ml$ did not affect 3T3-L1 cell viability. A CFEO concentration of between 0.1 and $1{\mu}g/ml$ significantly inhibited lipid accumulation during MDI-induced differentiation in 3T3-L1 cells in a dose-dependent manner, reaching a maximal level at $1{\mu}g/ml$ ($28.94{\pm}2.01%$; approximately 30% of control treated with MDI alone). Western blot analysis revealed that CFEO concentrations between 0.1 and $1{\mu}g/ml$ suppressed the activations of three adipogenic transcription factors in the MDI-stimulated 3T3-L1 cells: peroxisome proliferator-activated receptor ${\gamma}$; CCATT/enhancer binding protein ${\alpha}$; and sterol regulatory element binding protein-1. Moreover, the expressions of lipogenic enzymes, acetyl-CoA carboxylase, and fatty acid synthase were also inhibited by treatment with CFEO between 0.1 and $1{\mu}g/ml$. CFEO may therefore be a promising functional material for obesity prevention.
This study was performed in order to investigate the anti-obesity effect of Polygala tenuifolia on lipid mechanism in 3T3-L1 adipocytes. The chemical composition of the P. tenuifolia was analyzed in order to assess its nutritional value. Total dietary fiber was the highest among the proximate component of the P. tenuifolia. These results showed that the P. tenuifolia may be used as a potential functional ingredient for anti-obesity effect. Intracellular lipid droplets in the adipocyte were stained with oil-red O dye and quantified. In comparison to the control, lipid accumulation was significantly decreased by 40.1% and 22.4% when treated with the water extract and 70% EtOH extract of the P. tenuifolia at the concentration of $10{\mu}g/mL$, respectively. The anti-adipogenic effect of the water extract was stronger than that of the 70% EtOH extract. The gene expression levels were measured via Western blot and real-time PCR. As a result, the water extract was found to have decrease the gene expression of SREBP-1c, PPAR, $C/EBP{\alpha}$, FAS, ACC in a dose-dependent manner. These indicate that the water extract inhibits pre-adipocyte differentiation and adipogenesis by blocking the SREBP-1c gene expression in 3T3-L1 cells. Therefore, P. tenuifolia can be used as an effective anti-obesity agent.
Jung, Ho-Kyung;Sim, Mi-Ok;Jang, Ji-Hun;Kim, Tae-Muk;An, Byeong-Kwan;Kim, Min-Suk;Jung, Won Seok
Korean Journal of Plant Resources
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v.29
no.1
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pp.1-10
/
2016
Obesity is a pro-inflammatory state that contributes to the development of metabolic disorders such as hyperlipidemia, insulin resistance, type 2 diabetes, non-alcoholic fatty liver, and cardiovascular disease. In this study, we evaluated the inhibition of adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice by Peucedanum japonicum Thunberg L. water extract (PJT). Lipid accumulation measurement indicates that PJT markedly inhibited adipogenesis in a dose-dependent manner. RT-PCR results demonstrated that the mRNA expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α (C/EBPα) in 3T3-L1 cells were significantly down-regulated by PJT treatment. Oral administration of PJT (100, 300, and 500 ㎎/㎏, b.w/daily for 4 weeks) was conducted in high-fat diet induced obese mice and C57BL/6 mice. The PJT-administered group of HFD-induced mice had a lower body weight gain, along with decreased serum levels of glucose, triglycerides, and total cholesterol compared with the control mice, however, the HDL-cholesterol/total cholesterol ratio was increased. Furthermore, the elevated mRNA expression levels of adipogenesis related genes in the white adipose tissue of obese mice were significantly suppressed by PJT. These results indicate that PJT exhibits anti-obesity effects in obese mice by decreasing in serum lipid levels and lipogenesis related gene.
Purpose: The objective of this study was to examine whether Hamcho freeze-dried powder and Hamcho freeze-dried nano powder have an anti-obese effect on high fat diet-induced obese rats. Methods: Sprague Dawley rats were divided into 6 different groups, each of which was bred for 8 weeks with a different experimental diet: normal diet group (NC), high fat diet group (HFC), high fat diet + 2% Salicornia herbacea L. freeze-dried powder group (2% HS), high fat diet + 5% Salicornia herbacea L. freeze-dried powder group (5%HS), high fat diet + 1% Salicornia herbacea L. freeze-dried nano powder group (1% HSN), high fat diet + 2% Salicornia herbacea L. freeze-dried nano powder group (2% HSN). Results: The 5% HS group showed a weight loss effect in body weight, liver and adipose tissue by reducing the amount of dietary intake and food efficiency ratio. In addition, the 5% HS group showed a significant reduction of serum leptin concentration, while having a beneficial effect on the improvement of lipid metabolism such as increase the serum concentration of adiponectin. However, Hamcho freeze-dried nano powder did not show a weight loss effect. Conclusion: Overall data indicated that Hamcho seemed to have anti-obesity effects. In particular, consumption of 5% Hamcho freeze-dried powder might have beneficial effects on body weight, serum adiponectin level, and lipid profiles since it led to reduced body weight and growth of adipose tissues by suppressing dietary intakes. However conduct of further research studies is needed for analysis of active components and biochemical action mechanism of Hamcho.
We evaluated the effects of the partial dietary replacement of fish meal with squid liver $Meal^{TM}$ on the growth and body composition of juvenile olive flounder Paralichthys olivaceus during the winter season. Twenty-five fish with an initial body weight of 23 g per tank were distributed among 12,250 L flow-through tanks. The experimental diets, which were designated SLM5, SLM1O, and SLM15 diets, were prepared in triplicate along with control diet by replacing 5, 10, and $15\%$ of mackerel fish meal with squid liver $Meal^{TM}$, respectively. The weight gain and specific growth rate of flounder that were fed the control and SLM5 diets did not differ from those of the fish fed the SLM10 diet, but they were significantly (P<0.05) higher than those of the fish fed the SLM15 diet. The feed efficiency ratios for the flounder that were fed the control, SLM5 and SLM10 diets were significantly (P<0.05) higher than for the fish that were fed the SLM15 diet. However, the protein efficiency ratio for the flounder was not significantly affected by the experimental diets. The crude protein, crude lipid and ash content, and blood chemistry of the flounder were not significantly affected by the experimental diets. Therefore, the replacement of up to $10\%$ of dietary fish meal with squid liver $Meal^{TM}$ can be made without a reduction in growth or a deterioration of the feed efficiency of juvenile olive flounder during the winter season.
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